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Guo Y, Liu Z, Wang J, Deng X, He L, Zhang Y, Liu H, Qiu J. Equol neutralizes toxin B to combat Clostridioides difficile infection without disrupting the gut microbiota. Microbiol Res 2025; 298:128219. [PMID: 40378594 DOI: 10.1016/j.micres.2025.128219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 05/09/2025] [Accepted: 05/09/2025] [Indexed: 05/19/2025]
Abstract
Clostridioides difficile (C. difficile) toxin B (TcdB) is essential for C. difficile pathogenicity. TcdB induces apoptosis in host cells by internalizing and utilizing its glycosyltransferase activity to modify members of the small GTPase protein family through glycosylation. The intestinal environment is critical for the colonization of C. difficile, and the use of broad-spectrum antibiotics disrupts the balance of the gut microbiota, leading to increased susceptibility of the host to C. difficile. At present, the mainstream clinical approach for treating C. difficile infection (CDI) involves antibiotic therapies such as vancomycin, which disrupt the gut microbiota and are associated with a considerable risk of infection recurrence. Therefore, there is an urgent clinical need to develop new strategies to combat CDI. Here, we have identified a natural compound, equol, which inhibits the TcdB-mediated glycosylation of Rac1 through direct interaction, thereby reducing TcdB-induced cell death. Equol functions as an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), effectively suppressing the conversion of tryptophan to kynurenine in the intestinal tract while preserving the integrity of the gut microbiota. Concurrently, equol exhibits robust antioxidant properties, which markedly reduced TcdB-mediated oxidative damage and subsequent cell death. These findings suggest that equol holds therapeutic potential for the treatment of CDI.
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Affiliation(s)
- Yan Guo
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Zhiying Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Jianfeng Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xuming Deng
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Liuqing He
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Yong Zhang
- Center for Pathogen Biology and Infectious Diseases, State Key Laboratory for Zoonotic Diseases, The First Hospital of Jilin University, Changchun, China.
| | - Hongtao Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
| | - Jiazhang Qiu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.
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Yang Y, Ning Y, Chen Y, Tian T, Gao X, Kong Y, Lei K, Cui Z. Transferrin Receptor Promotes Endometrial Cancer Proliferation by Activating the Iron-Dependent PI3K/AKT/mTOR Signaling Pathway. Cancer Sci 2025; 116:1352-1365. [PMID: 40022544 PMCID: PMC12044649 DOI: 10.1111/cas.70015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 01/22/2025] [Accepted: 01/29/2025] [Indexed: 03/03/2025] Open
Abstract
Aberrant iron metabolism is frequently observed in cancers, including endometrial cancer (EC). However, the role of transferrin receptor (TFRC), a key regulator of iron metabolism, remains unclear in endometrial cancer. We found transferrin receptor expression was significantly upregulated in endometrial cancer tissues compared to adjacent nontumor tissues, and high transferrin receptor levels were associated with poor prognosis. Functional studies revealed that transferrin receptor knockdown impaired endometrial cancer cell proliferation in vitro and in vivo, while transferrin receptor overexpression enhanced endometrial cancer cell proliferation. Mechanistically, transferrin receptor activated the PI3K/AKT/mTOR signaling pathway, as its knockdown suppressed the pathway, and rapamycin, an mTOR inhibitor, reversed transferrin receptor-induced pathway activation and proliferation. Modulation of the labile iron pool by ferric ammonium citrate (FAC) or deferoxamine (DFO) rescued transferrin receptor-induced biological effects. Additionally, AURKA was identified as a regulator of transferrin receptor expression. These findings demonstrate the oncogenic role of transferrin receptor in endometrial cancer and suggest that targeting iron homeostasis and the PI3K/AKT/mTOR pathway may represent potential therapeutic strategies for endometrial cancer.
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Affiliation(s)
- Yufei Yang
- Department of Clinical MedicineQingdao UniversityQingdaoChina
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Ying Ning
- Center of Tumor Immunology and Cytotherapy, Medical Research CenterThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Yu Chen
- Department of Clinical MedicineQingdao UniversityQingdaoChina
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Tian Tian
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Xinyan Gao
- Department of Clinical MedicineQingdao UniversityQingdaoChina
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Yan Kong
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Ke Lei
- Center of Tumor Immunology and Cytotherapy, Medical Research CenterThe Affiliated Hospital of Qingdao UniversityQingdaoChina
| | - Zhumei Cui
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
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Sánchez-Terrón G, Martínez R, Freire MJ, Molina-Infante J, Estévez M. Gastrointestinal fate of proteins from commercial plant-based meat analogs: Silent passage through the stomach, oxidative stress in intestine, and gut dysbiosis in Wistar rats. J Food Sci 2024; 89:10294-10316. [PMID: 39475341 DOI: 10.1111/1750-3841.17458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/16/2024] [Accepted: 09/24/2024] [Indexed: 12/28/2024]
Abstract
Plant-based meat analogs (PBMAs) are common ultra-processed foods (UPFs) included in the vegan/vegetarian diets as presumed healthy alternatives to meat and meat products. However, such health claims need to be supported by scientific evidence. To gain further insight into this topic, two commercial UPFs typically sold as meat analogs, namely, seitan (S) and tofu (T), were included in a cereal-based chow and provided to Wistar rats for 10 weeks. A group of animals had, simultaneously, an isocaloric and isoprotein experimental diet formulated with cooked beef (B). In all cases, experimental chows (∼4 kcal/g feed) had their basal protein concentration increased from 14% to 30% using proteins from S, T, or B. Upon slaughter, in vivo protein digestibility was assessed, and the entire gastrointestinal tract (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Metagenomics was also applied to assess the variation of microbiota composition as affected by dietary protein. Diets based on PBMAs showed lower protein digestibility than those containing meat and promoted an intense luminal glycoxidative stress and an inflammatory intestinal response. The fermentation of undigested oxidized proteins from T in the colon of Wistar rats likely led to formation of mutagenic metabolites such as p-cresol. The presence of these compounds in the animal models raises concerns about the potential effects of full replacement of meat by certain PBMAs in the diet. Therefore, future research might target on translational human studies to shed light on these findings.
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Affiliation(s)
- G Sánchez-Terrón
- TECAL Research Group, Meat and Meat Products Research Institute (IPROCAR), Universidad de Extremadura (UEX), Cáceres, Spain
| | - R Martínez
- TECAL Research Group, Meat and Meat Products Research Institute (IPROCAR), Universidad de Extremadura (UEX), Cáceres, Spain
- Animal Health Department, Animal Health and Zoonoses Research Group (GISAZ), UIC Zoonosis and Emergent Diseases (ENZOEM Competitive Research Unit), Universidad of Córdoba (UCO, ROR-ID 05yc77b46), Córdoba, Spain
| | - M J Freire
- Meat Quality Area, Center of Scientific and Technological Research of Extremadura (CICYTEX-La Orden), Junta de Extremadura, Guadajira, Badajoz, Spain
| | - J Molina-Infante
- Gastroenterology Department, Hospital Universitario Cácerses, Servicio Extremeño de Salud, Cáceres, Spain
| | - M Estévez
- TECAL Research Group, Meat and Meat Products Research Institute (IPROCAR), Universidad de Extremadura (UEX), Cáceres, Spain
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Maleki M, Tabnak P, Golchin A, Yousefi B, Nazari A. Resveratrol inhibited colorectal cancer progression by reducing oxidative DNA damage by targeting the JNK signaling pathway. Heliyon 2024; 10:e38631. [PMID: 39524725 PMCID: PMC11550663 DOI: 10.1016/j.heliyon.2024.e38631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 08/15/2024] [Accepted: 09/26/2024] [Indexed: 11/16/2024] Open
Abstract
Recent evidence has proved that resveratrol as a natural polyphenol has great anti-cancer and anti-proliferative effects in cancer cells. In this study, we aimed to examine the protective effects of resveratrol in rats with 1,2-dimethylhydrazine (DMH)-induced colorectal cancer and investigate the potential underlying molecular mechanisms. Male Wistar rats were classified into different groups, including Group 1 without any intervention, group 2 as resveratrol-received rats (8 mg/kg), Group 3 as DMH-received rats, and Group 4, as DMH and resveratrol-received rats. DNA damage, DNA repair, the expression levels and activities of antioxidants, and JNK signaling were evaluated in colon tissues. We found that DNA damage and DNA repair were significantly suppressed and induced, respectively, in DMH + resveratrol groups. The expression levels and activities of antioxidants were increased in DMH + resveratrol groups. Lipid and protein peroxidation were significantly suppressed in DMH + resveratrol groups. In addition, resveratrol also modulated JNK signaling in DMH + resveratrol groups. Our findings demonstrated that resveratrol effectively reversed DMH-mediated oxidative stress and DNA damage by targeting the JNK signaling pathway.
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Affiliation(s)
- Masoumeh Maleki
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Peyman Tabnak
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Asal Golchin
- Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Bahman Yousefi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmad Nazari
- Tehran University of Medical Sciences, Tehran, Iran
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Sawai K, Goi T, Kimura Y, Koneri K. Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection. Cancers (Basel) 2024; 16:3550. [PMID: 39456644 PMCID: PMC11505646 DOI: 10.3390/cancers16203550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/16/2024] [Accepted: 10/18/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. METHODS This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. RESULTS The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p < 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. CONCLUSIONS These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.
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Affiliation(s)
- Katsuji Sawai
- First Department of Surgery, University of Fukui, Fukui 910-1193, Japan; (T.G.); (Y.K.); (K.K.)
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Sawicka D, Maciak S, Sadowska A, Sokołowska E, Gohal S, Guzińska-Ustymowicz K, Niemirowicz-Laskowska K, Car H. Metabolic Rate and Oxidative Stress as a Risk Factors in the Development of Colorectal Cancer. Int J Mol Sci 2024; 25:10713. [PMID: 39409042 PMCID: PMC11476475 DOI: 10.3390/ijms251910713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 09/30/2024] [Accepted: 10/03/2024] [Indexed: 10/20/2024] Open
Abstract
There is growing evidence that the body's energy expenditures constitute a significant risk factor for the development of most deadly diseases, including cancer. Our aim was to investigate the impact of basal metabolic rate (BMR) on the growth and progression of colorectal cancer (CRC). To do so, we used a unique model consisting of three lines of laboratory mice (Mus musculus) artificially selected for high (HBMR) and low (LBMR) basal metabolic rate and randomly bred individuals (non-selected, NSBMR). The experimental individuals were implanted with human colorectal cancer cells DLD-1. The variation in BMR between the lines allowed for testing the impact of whole-body metabolism on oxidative and antioxidant parameters in the liver throughout the cancerogenesis process. We investigated the dependence between metabolic values, reactive oxygen species (ROS) levels, and Kelch-like ECH-associated protein 1-based E3 ligase complexes (Keap1) gene activity in these animals. We found that the HBMR strain had a higher concentration of oxidative enzymes compared to the LBMR and NSBMR. Furthermore, the growth rate of CRC tumors was associated with alterations in the levels of oxidative stress enzymes and Keap1 expression in animals with a high metabolic rate. Our results indicate that a faster growth and development of CRC line DLD-1 is associated with enzymatic redox imbalance in animals with a high BMR.
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Affiliation(s)
- Diana Sawicka
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland; (A.S.); (S.G.); (K.N.-L.); (H.C.)
| | - Sebastian Maciak
- Department of Evolutionary and Physiological Ecology, Faculty of Biology, University of Bialystok, Ciolkowskiego Street 1J, 15-245 Bialystok, Poland;
| | - Anna Sadowska
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland; (A.S.); (S.G.); (K.N.-L.); (H.C.)
| | - Emilia Sokołowska
- Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona Street 15A, 15-274 Bialystok, Poland;
| | - Sylwia Gohal
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland; (A.S.); (S.G.); (K.N.-L.); (H.C.)
| | - Katarzyna Guzińska-Ustymowicz
- Department of General Pathomorphology, Medical University of Bialystok, Waszyngtona Street 13, 15-269 Bialystok, Poland;
| | - Katarzyna Niemirowicz-Laskowska
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland; (A.S.); (S.G.); (K.N.-L.); (H.C.)
| | - Halina Car
- Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland; (A.S.); (S.G.); (K.N.-L.); (H.C.)
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Gharib E, Robichaud GA. From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies. Int J Mol Sci 2024; 25:9463. [PMID: 39273409 PMCID: PMC11395697 DOI: 10.3390/ijms25179463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/19/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma-carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.
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Affiliation(s)
- Ehsan Gharib
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
| | - Gilles A Robichaud
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
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González A, Fullaondo A, Odriozola A. Microbiota-associated mechanisms in colorectal cancer. ADVANCES IN GENETICS 2024; 112:123-205. [PMID: 39396836 DOI: 10.1016/bs.adgen.2024.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking third in terms of incidence and second as a cause of cancer-related death. There is growing scientific evidence that the gut microbiota plays a key role in the initiation and development of CRC. Specific bacterial species and complex microbial communities contribute directly to CRC pathogenesis by promoting the neoplastic transformation of intestinal epithelial cells or indirectly through their interaction with the host immune system. As a result, a protumoural and immunosuppressive environment is created conducive to CRC development. On the other hand, certain bacteria in the gut microbiota contribute to protection against CRC. In this chapter, we analysed the relationship of the gut microbiota to CRC and the associations identified with specific bacteria. Microbiota plays a key role in CRC through various mechanisms, such as increased intestinal permeability, inflammation and immune system dysregulation, biofilm formation, genotoxin production, virulence factors and oxidative stress. Exploring the interaction between gut microbiota and tumourigenesis is essential for developing innovative therapeutic approaches in the fight against CRC.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
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Fan C, Yang X, Yan L, Shi Z. Oxidative stress is two-sided in the treatment of acute myeloid leukemia. Cancer Med 2024; 13:e6806. [PMID: 38715546 PMCID: PMC11077289 DOI: 10.1002/cam4.6806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/14/2023] [Accepted: 11/27/2023] [Indexed: 05/12/2024] Open
Abstract
INTRODUCTION Oxidative stress caused by elevated ROS, as a novel therapeutic mechanism, has been implicated in various tumors including AML. AML cells are chronically under oxidative stress, yet overreliance on ROS production makes tumor cells increasingly vulnerable to further damage. Reducing the cytotoxic effect of ROS on normal cells while killing leukemia stem cell (LSC) with high levels of reactive oxygen species is a new challenge for oxidative stress therapy in leukemia. METHODS By searching literature databases, we summarized recent relevant studies. The relationship of ROS on AML genes, signaling pathways, and transcription factors, and the correlation of ROS with AML bone marrow microenvironment and autophagy were summarized. In addition, we summarize the current status of research on ROS and AML therapeutics. Finally, we discuss the research progress on redox resistance in AML. RESULTS This review discusses the evidence showing the link between redox reactions and the progression of AML and compiles the latest research findings that will facilitate future biological studies of redox effects associated with AML treatment. CONCLUSION We believe that exploiting this unique oxidative stress property of AML cells may provide a new way to prevent relapse and drug resistance.
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Affiliation(s)
- Chenyang Fan
- First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina
- National Clinical Research Center for Chinese Medicine Acupuncture and MoxibustionTianjinChina
| | - Xiangdong Yang
- First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina
- National Clinical Research Center for Chinese Medicine Acupuncture and MoxibustionTianjinChina
| | - Lixiang Yan
- First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina
- National Clinical Research Center for Chinese Medicine Acupuncture and MoxibustionTianjinChina
| | - Zhexin Shi
- First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina
- National Clinical Research Center for Chinese Medicine Acupuncture and MoxibustionTianjinChina
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Wang F, Xu WQ, Zhang WQ, Xu RC, Sun JL, Zhang GC, Liu ZY, Qi ZR, Dong L, Weng SQ, Shen XZ, Liu TT, Fang Y, Zhu JM. Transferrin receptor 1 promotes hepatocellular carcinoma progression and metastasis by activating the mTOR signaling pathway. Hepatol Int 2024; 18:636-650. [PMID: 37982952 DOI: 10.1007/s12072-023-10607-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 10/09/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND Aberrant iron metabolism is commonly observed in multiple tumor types, including hepatocellular carcinoma (HCC). However, as the key regulator of iron metabolism involved in iron absorption, the role of transferrin receptor (TFRC) in HCC remains elusive. METHODS The mRNA and protein expression of TFRC were evaluated in paired HCC and adjacent non-tumor specimens. The correlation between TFRC level and clinicopathological features or prognostic significance was also analyzed. The role of TFRC on biological functions was finally studied in vitro and in vivo. RESULTS The TFRC level was remarkably upregulated in HCC tissues compared to paired peritumor tissues. Overexpressed TFRC positively correlated with serum alpha-fetoprotein, carcinoembryonic antigen, and poor tumor differentiation. Multivariate analysis demonstrated that upregulated TFRC was an independent predictive marker for poorer overall survival and disease-free survival in HCC patients. Loss of TFRC markedly impaired cell proliferation and migration in vitro and notably suppressed HCC growth and metastasis in vivo, while overexpression of TFRC performed an opposite effect. Mechanistically, the mTOR signaling pathway was downregulated with TFRC knockdown, and the mTOR agonist MHY1485 completely reversed the biological inhibition in HCC cells caused by TFRC knockdown. Furthermore, exogenous ferric citrate (FAC) or iron chelator reversed the changed biological functions and signaling pathway expression of HCC cells caused by TFRC knockdown or overexpression, respectively. CONCLUSIONS Our study indicates that TFRC exerts an oncogenic role in HCC and may become a promising therapeutic target to restrain HCC progression.
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Affiliation(s)
- Fu Wang
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Wei-Qi Xu
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wan-Qin Zhang
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Ru-Chen Xu
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Jia-Lei Sun
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Guang-Cong Zhang
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Zhi-Yong Liu
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Zhuo-Ran Qi
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Ling Dong
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Shu-Qiang Weng
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Xi-Zhong Shen
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
- Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, 138 Yixueyuan Rd., Shanghai, 200032, China
| | - Tao-Tao Liu
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China
| | - Ying Fang
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
| | - Ji-Min Zhu
- Department of Gastroenterology and Hepatology and Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
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Brzozowa-Zasada M, Piecuch A, Bajdak-Rusinek K, Michalski M, Klymenko O, Matysiak N, Janelt K, Czuba Z. Glutathione Reductase Expression and Its Prognostic Significance in Colon Cancer. Int J Mol Sci 2024; 25:1097. [PMID: 38256170 PMCID: PMC10816751 DOI: 10.3390/ijms25021097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 01/09/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Maintaining a balanced redox state within cells is crucial for the sustenance of life. The process involves continuous cytosolic disulfide reduction reactions to restore oxidized proteins to their reduced thiol forms. There are two main cellular antioxidant pathways-the thioredoxin (Trx) and glutathione (GSH)/glutaredoxin (Grx) systems. In the GSH/Grx system, glutathione reductase (GR; GSR) catalyses the reduction of GSH disulfide (GSSG) to its sulfhydryl form (GSH), which can then further reduce oxidized Grxs. GR is an essential enzyme that helps in maintaining the supply of reduced glutathione-GSH, which is a significant reducing thiol found in most cells and known for its antioxidant properties. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of GR protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The results of our study revealed a significant relationship between the immunohistochemical expression of GR and tumour histological grade, depth of invasion, regional lymph node involvement, staging, and PCNA immunohistochemical expression. It was found that 95% of patients with stage I had low levels of GR expression, whereas 89% of patients with stage III had high levels of immunohistochemical expression. A high level of expression was also detected in the patients with stage II of the disease, where almost 63% were characterized by a high expression of GR. The Western blot method revealed that the highest level of expression was found in the LS 174T cell line, which corresponds to stage II. The results of our study indicate that the immunohistochemical expression of GR may act as an independent prognostic factor associated with colon adenocarcinoma patients' prognosis.
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Affiliation(s)
- Marlena Brzozowa-Zasada
- Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Adam Piecuch
- Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Karolina Bajdak-Rusinek
- Department of Medical Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Marek Michalski
- Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
- Zabrze Silesian Nanomicroscopy Centre in Zabrze, Silesia LabMed—Research and Implementation Centre, Medical University of Silesia, 40-055 Katowice, Poland
| | - Olesya Klymenko
- Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Natalia Matysiak
- Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Kamil Janelt
- Department of Medical Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Zenon Czuba
- Department of Microbiology and Immunology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland
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12
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Saeed RF, Awan UA, Aslam S, Qazi AS, Bhatti MZ, Akhtar N. Micronutrients Importance in Cancer Prevention-Minerals. Cancer Treat Res 2024; 191:145-161. [PMID: 39133407 DOI: 10.1007/978-3-031-55622-7_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
Cancer, a non-communicable disease with diverse kinds is one of the major global problems with high incidence and no proven method to prevent or treat. Minerals including trace elements are significant micronutrients for preserving the body's typical physiological function. In contrast to extremely processed industrial food, they are rich in natural sources of food and frequently included in nutritional supplements. The daily intake, storage capacities, and homeostasis of micronutrients depend on specific dietary practices in contemporary civilization and can be disturbed by various malignancies. Varied minerals have different effects on the status of cancer depending on how they affect these pathways. The outcomes could differ depending on the mineral such as calcium's supply and the cancer's location. A mineral called zinc helps the immune system function better and aids in wound healing. On the other hand, selenium exhibits anti-oxidant functions and has a dose-response relationship with many cancer types. However, this component can make the patient's condition worse. Although the body produces free radicals when iron is deficient, anaemia affects a patient's quality of life and ability to receive therapy. This chapter compiles the knowledge of minerals connected to unusual accumulation or depletion states in various malignancies.
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Affiliation(s)
- Rida Fatima Saeed
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan.
| | - Uzma Azeem Awan
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
| | - Shaista Aslam
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
| | - Asma Saleem Qazi
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
| | - Muhammad Zeeshan Bhatti
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
| | - Nosheen Akhtar
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan
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13
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Abbasi M, Yazdanirad S, Dehdarirad H, Hughes D. Noise exposure and the risk of cancer: a comprehensive systematic review. REVIEWS ON ENVIRONMENTAL HEALTH 2023; 38:713-726. [PMID: 36064622 DOI: 10.1515/reveh-2022-0021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 08/14/2022] [Indexed: 06/15/2023]
Abstract
The association between noise exposure and increased risk of cancer has received little attention in the field of research. Therefore, the goal of this study was to conduct a systematic review on the relationship between noise exposure and the incidence of cancer in humans. In this study, four electronic bibliographic databases including Scopus, PubMed, Web of Science, and Embase were systematically searched up to 21 April 2022. All types of noise exposure were considered, including environmental noise, occupational noise, and leisure or recreational noise. Furthermore, all types of cancers were studied, regardless of the organs involved. In total, 1836 articles were excluded on the basis of containing exclusion criteria or lacking inclusion criteria, leaving 19 articles retained for this study. Five of nine case-control studies showed a significant relationship between occupational or leisure noise exposure and acoustic neuroma. Moreover, four of five case-control and cohort studies indicated statistically significant relationships between environmental noise exposure and breast cancer. Of other cancer types, two case-control studies highlighted the risk of Hodgkin and non-Hodgkin lymphoma and two cohort studies identified an increased risk of colon cancer associated with environmental noise exposure. No relationship between road traffic and railway noise and the risk of prostate cancer was observed. In total, results showed that noise exposure, particularly prolonged and continuous exposure to loud noise, can lead to the incidence of some cancers. However, confirmation of this requires further epidemiological studies and exploration of the exact biological mechanism and pathway for these effects.
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Affiliation(s)
- Milad Abbasi
- Occupational Health Engineering, Social Determinants of Health Research Center, Saveh University of Medical Sciences, Saveh, Iran
| | - Saeid Yazdanirad
- School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Social Determinants of Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hossein Dehdarirad
- Medical Library & Information Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Debra Hughes
- Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
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14
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Yuan K, Hu D, Mo X, Zeng R, Wu B, Zhang Z, Hu R, Wang C. Novel diagnostic biomarkers of oxidative stress, immune- infiltration characteristics and experimental validation of SERPINE1 in colon cancer. Discov Oncol 2023; 14:206. [PMID: 37980291 PMCID: PMC10657345 DOI: 10.1007/s12672-023-00833-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 11/15/2023] [Indexed: 11/20/2023] Open
Abstract
BACKGROUND Colon cancer (CC) is a prevalent malignant tumor that affects the colon in the gastrointestinal tract. Its aggressive nature, strong invasiveness, and rapid progression make it a significant health concern. In addition, oxidative stress can lead to the production of reactive oxygen species (ROS) that surpass the body's antioxidant defense capacity, causing damage to proteins, lipids, and DNA, potentially promoting tumor development. However, the relationship between CC and oxidative stress requires further investigation. METHODS We collected gene expression data and clinical data from 473 CC patients from The Cancer Genome Atlas (TCGA) dataset. Additionally, we obtained 433 oxidative stress genes from Genecards ( https://www.genecards.org/ ). Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients. To validate the models, we utilized data from the Gene Expression Omnibus (GEO) database. We assessed the accuracy of the models through various techniques, including the creation of a nomogram, receiver operating characteristic curve (ROC) analysis, and principal component analysis (PCA). The Cytoscape program was utilized to identify hub genes among differentially expressed genes (DEGs) in tumor patients using the TCGA dataset. Subsequently, we conducted survival analysis, clinical relevance analysis, and immune cell relevance analysis for the intersected genes obtained by combining the hub genes with the genes from the predictive models. Moreover, we investigated the mRNA expression and potential functions of these intersected genes using a range of experimental approaches. RESULTS In both the TCGA and GSE17538 datasets, patients classified as high-risk had significantly shorter overall survival compared to those in the low-risk group (TCGA: p < 0.001; GSE17538: p = 0.010). As a result, we decided to further investigate the role of SERPINE1. Our survival analysis revealed that patients with high expression of SERPINE1 had a significantly lower probability of survival compared to those with low expression (p < 0.05). Additionally, our clinical correlation analysis showed a significant relationship between SERPINE1 expression and T, N, and M stages, as well as tumor grade. Furthermore, our immune infiltration correlation analysis demonstrated notable differences in multiple immune cells between the high- and low-expression groups of SERPINE1. To validate our findings, we conducted experimental tests and observed that knocking down SERPINE1 in colon cancer cells resulted in significant reductions in cell viability and proliferation. Interestingly, we also noticed an increase in oxidative stress parameters, such as ROS and MDA levels, while the levels of reduced GSH decreased upon SERPINE1 knockdown. These findings suggest that the antineoplastic effect of silencing SERPINE1 may be associated with the induction of oxidative stress. CONCLUSION In conclusion, this study introduces a new approach for the early diagnosis and treatment of CC, and further exploration of SERPINE1 could potentially lead to a significant advancement.
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Affiliation(s)
- Kaisheng Yuan
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China
- The Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine, Jinan University, Guangzhou, 510000, Guangdong, China
| | - Di Hu
- Department of Neurology and Stroke Centre, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China
| | - Xiaocong Mo
- Department of Oncology, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China
| | - Ruiqi Zeng
- Department of Urology, the Second People's Hospital of Yibin City, Yibin, 644000, Sichuan, China
| | - Bing Wu
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China
- The Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine, Jinan University, Guangzhou, 510000, Guangdong, China
| | - Zunhao Zhang
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China
| | - Ruixiang Hu
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China.
- The Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine, Jinan University, Guangzhou, 510000, Guangdong, China.
| | - Cunchuan Wang
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510000, Guangdong, China.
- The Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine, Jinan University, Guangzhou, 510000, Guangdong, China.
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15
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Miladinov M, Rosic J, Eric K, Guzonjic A, Jelenkovic J, Bogavac-Stanojevic N, Dimitrijevic I, Kotur-Stevuljevic J, Barisic G. Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients. Int J Mol Sci 2023; 24:15083. [PMID: 37894765 PMCID: PMC10606719 DOI: 10.3390/ijms242015083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/13/2023] [Accepted: 09/20/2023] [Indexed: 10/29/2023] Open
Abstract
The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.
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Affiliation(s)
- Marko Miladinov
- Clinic for Digestive Surgery-First Surgical Clinic, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Jovana Rosic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Katarina Eric
- Department of Pathology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Azra Guzonjic
- Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
| | - Jelenko Jelenkovic
- Clinic for Digestive Surgery-First Surgical Clinic, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | | | - Ivan Dimitrijevic
- Clinic for Digestive Surgery-First Surgical Clinic, University Clinical Center of Serbia, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | | | - Goran Barisic
- Clinic for Digestive Surgery-First Surgical Clinic, University Clinical Center of Serbia, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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16
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Ephraim R, Fraser S, Devereaux J, Stavely R, Feehan J, Eri R, Nurgali K, Apostolopoulos V. Differential Gene Expression of Checkpoint Markers and Cancer Markers in Mouse Models of Spontaneous Chronic Colitis. Cancers (Basel) 2023; 15:4793. [PMID: 37835487 PMCID: PMC10571700 DOI: 10.3390/cancers15194793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/17/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.
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Affiliation(s)
- Ramya Ephraim
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (R.E.); (S.F.); (J.D.); (J.F.); (K.N.)
| | - Sarah Fraser
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (R.E.); (S.F.); (J.D.); (J.F.); (K.N.)
| | - Jeannie Devereaux
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (R.E.); (S.F.); (J.D.); (J.F.); (K.N.)
| | - Rhian Stavely
- Pediatric Surgery Research Laboratories, Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA;
| | - Jack Feehan
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (R.E.); (S.F.); (J.D.); (J.F.); (K.N.)
- Immunology Program, Australian Institute of Musculoskeletal Science (AIMSS), Melbourne, VIC 3021, Australia
| | - Rajaraman Eri
- STEM/School of Science, RMIT University, Melbourne, VIC 3001, Australia;
| | - Kulmira Nurgali
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (R.E.); (S.F.); (J.D.); (J.F.); (K.N.)
- Department of Medicine Western Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia
- Regenerative Medicine and Stem Cells Program, Australian Institute of Musculoskeletal Science (AIMSS), Melbourne, VIC 3021, Australia
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (R.E.); (S.F.); (J.D.); (J.F.); (K.N.)
- Immunology Program, Australian Institute of Musculoskeletal Science (AIMSS), Melbourne, VIC 3021, Australia
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17
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Bastin J, Sroussi M, Nemazanyy I, Laurent-Puig P, Mouillet-Richard S, Djouadi F. Downregulation of mitochondrial complex I induces ROS production in colorectal cancer subtypes that differently controls migration. J Transl Med 2023; 21:522. [PMID: 37533102 PMCID: PMC10398918 DOI: 10.1186/s12967-023-04341-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 07/10/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) can be classified into four molecular subtypes (CMS) among which CMS1 is associated with the best prognosis, while CMS4, the mesenchymal subtype, has the worst outcome. Although mitochondria are considered to be hubs of numerous signaling pathways, the study of mitochondrial metabolism has been neglected for many years. Mitochondrial Complex I (CI) plays a dual role, both in energy and reactive oxygen species (ROS) production. However, the possible contribution of CI to tumorigenesis in cancer remains unclear. The purpose of this study was to investigate the CI under the prism of the CMS classification of CRC in ex vivo models. METHODS Biochemical dosages, bioenergetics analysis and western-blot were used to characterize CI expression, function and redox balance in LoVo and MDST8 cell lines, belonging to CMS1 and CMS4 subgroups, respectively. Cell proliferation and migration were assessed by xCELLigence technology. Overproduction or scavenging of mitochondrial ROS (mtROS) were performed to analyze the effect of mtROS on proliferation, migration, and mesenchymal markers. Focal adhesion kinase (FAK) and its activation were analyzed by immunofluorescence. We assessed the distribution of two CI scores in CRC cohorts according to CMS classification and their relevance for patient survival. RESULTS We found that CI is downregulated in CMS4 cells and is associated with elevated mtROS. We establish for the first time that in these migrating cells, mtROS production is maintained at optimal levels not only through changes in CI activity but also by inactivation/acetylation of superoxide dismutase 2 (SOD2), a major mitochondrial antioxidant enzyme. We show that promoting or scavenging mtROS both mitigate CMS4 cells' migration. Our results also point to a mtROS-mediated focal adhesion kinase (FAK) activation, which likely sustains their migratory phenotype. Using cohorts of CRC patients, we document that the expression of CI is downregulated in the CMS4 subgroup, and that low CI expression is associated with poor prognosis. Patients' datasets reveal an inverse correlation between CI and the epithelial-mesenchymal transition (EMT) pathway. CONCLUSION We showed that inhibition of CI contributes to heighten mtROS, which likely foster MDST8 migration and might account for the specific EMT signature of CMS4 tumors. These data reveal a novel role of mitochondrial CI in CRC, with biological consequences that may be targeted with anti- or pro-oxidant drugs in clinical practice.
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Affiliation(s)
- Jean Bastin
- Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université Paris-Cité, 15, Rue de l'Ecole de Médecine, 75006, Paris, France
| | - Marine Sroussi
- Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université Paris-Cité, 15, Rue de l'Ecole de Médecine, 75006, Paris, France
- Laboratoire de Biochimie, Ecole Supérieure de Physique et de Chimie Industrielle de la Ville de Paris, 75005, Paris, France
| | - Ivan Nemazanyy
- Plate Plateforme d'étude du Métabolisme, SFR Necker, INSERM US24/CNRS UAR3633, 75015, Paris, France
| | - Pierre Laurent-Puig
- Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université Paris-Cité, 15, Rue de l'Ecole de Médecine, 75006, Paris, France
- Institut du Cancer Paris CARPEM, Department of Biology Hôpital Georges Pompidou, 75015, Paris, France
| | - Sophie Mouillet-Richard
- Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université Paris-Cité, 15, Rue de l'Ecole de Médecine, 75006, Paris, France
| | - Fatima Djouadi
- Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université Paris-Cité, 15, Rue de l'Ecole de Médecine, 75006, Paris, France.
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18
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Duan B, Zhang H, Zhu Z, Yan X, Ji Z, Li J. LncRNA LINC01871 sponging miR-142-3p to modulate ZYG11B promotes the chemoresistance of colorectal cancer cells by inducing autophagy. Anticancer Drugs 2023; 34:827-836. [PMID: 36847071 PMCID: PMC10344439 DOI: 10.1097/cad.0000000000001478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 08/22/2022] [Indexed: 03/01/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) is a malignant tumor in the digestive tract. Increasing evidence indicated that chemoresistance leads to a poor prognosis of CRC. Herein, we aimed to uncover the potential mechanism by which long intergenic noncoding RNA-1871 (LINC01871) affects the chemoresistance of CRC cells. METHODS Relative level of LINC01871 in CRC tissues was assessed by reverse transcription quantitative PCR (RT-qPCR). Kaplan-Meier analysis was conducted to determine the relevance of LINC01871 and the prognosis of CRC patients. Cell Counting Kit-8 (CCK-8) and colony formation assay were used to evaluate the proliferation of SW480 cells. Expression levels of proteins and their genes were assessed by western blot, immunofluorescence staining and RT-qPCR. In addition, the interaction of LINC01871, miR-142-3p and protein zyg-11 homolog B (ZYG11B) were analyzed via dual-luciferase reporter assays. RESULTS LINC01871 was low-expressed in CRC tissues and cell lines. Patients with a low level of LINC01871 showed significantly lower survival rate. pcDNA-LINC01871 significantly reduced the viability of SW480 cells ( P < 0.01), elevated SW480 cells sensitivity to 5-FU ( P < 0.01), reduced LC3 punctate aggregates ( P < 0.01) and downregulated the relative mRNA expression level of autophagy related protein 9A, autophagy related protein 4B and high mobility group box 1 ( P < 0.01) in SW480 cells. Moreover, LINC01871 was found to sponge miR-142-3p, and ZYG11B was the target of miR-142-3p. MiR-142-3p mimic significantly recovered the effect of pcDNA-LINC001871, whereas pcDNA-ZYG11B reversed the recovery effect of the miR-142-3p mimic. CONCLUSION LINC01871/miR-142-3p/ ZYG11B axis regulates the chemoresistance of CRCs by inducing autophagy.
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Affiliation(s)
- Bensong Duan
- Department of Gastroenterology, Endoscopy Center
| | - Haibin Zhang
- Department of Gastroenterology, Endoscopy Center
| | | | - Xiaohan Yan
- Department of Gastroenterology, Endoscopy Center
| | - Zhonghua Ji
- Department of Anesthesia, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jingze Li
- Department of Gastroenterology, Endoscopy Center
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19
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Nguyen DD, Kim E, Le NT, Ding X, Jaiswal RK, Kostlan RJ, Nguyen TNT, Shiva O, Le MT, Chai W. Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair. SCIENCE ADVANCES 2023; 9:eadd8023. [PMID: 37163605 PMCID: PMC10171824 DOI: 10.1126/sciadv.add8023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 04/05/2023] [Indexed: 05/12/2023]
Abstract
Despite the high lethality of colorectal cancers (CRCs), only a limited number of genetic risk factors are identified. The mammalian ssDNA-binding protein complex CTC1-STN1-TEN1 protects genome stability, yet its role in tumorigenesis is unknown. Here, we show that attenuated CTC1/STN1 expression is common in CRCs. We generated an inducible STN1 knockout mouse model and found that STN1 deficiency in young adult mice increased CRC incidence, tumor size, and tumor load. CRC tumors exhibited enhanced proliferation, reduced apoptosis, and elevated DNA damage and replication stress. We found that STN1 deficiency down-regulated multiple DNA glycosylases, resulting in defective base excision repair (BER) and accumulation of oxidative damage. Collectively, this study identifies STN1 deficiency as a risk factor for CRC and implicates the previously unknown STN1-BER axis in protecting colon tissues from oxidative damage, therefore providing insights into the CRC tumor-suppressing mechanism.
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Affiliation(s)
- Dinh Duc Nguyen
- Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
| | - Eugene Kim
- Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
| | - Nhat Thong Le
- School of Biotechnology, International University, Ho Chi Minh City, Vietnam
| | - Xianzhong Ding
- Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
| | - Rishi Kumar Jaiswal
- Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
| | - Raymond Joseph Kostlan
- Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
| | - Thi Ngoc Thanh Nguyen
- Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
| | - Olga Shiva
- Office of Research, Washington State University-Spokane, Spokane, WA, USA
| | - Minh Thong Le
- School of Biotechnology, International University, Ho Chi Minh City, Vietnam
| | - Weihang Chai
- Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
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Chaudhary P, Janmeda P, Docea AO, Yeskaliyeva B, Abdull Razis AF, Modu B, Calina D, Sharifi-Rad J. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Front Chem 2023; 11:1158198. [PMID: 37234200 PMCID: PMC10206224 DOI: 10.3389/fchem.2023.1158198] [Citation(s) in RCA: 241] [Impact Index Per Article: 120.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 04/26/2023] [Indexed: 05/27/2023] Open
Abstract
Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are removed from the body by antioxidant processes. If these natural mechanisms are disrupted, radicals accumulate in excess and contribute to the development of many diseases. Methodology: Relevant recent information on oxidative stress, free radicals, reactive oxidative species, and natural and synthetic antioxidants was collected by researching electronic databases such as PubMed / Medline, Web of Science, and Science Direct. Results: According to the analysed studies, this comprehensive review provided a recent update on oxidative stress, free radicals and antioxidants and their impact on the pathophysiology of human diseases. Discussion: To counteract the condition of oxidative stress, synthetic antioxidants must be provided from external sources to supplement the antioxidant defense mechanism internally. Because of their therapeutic potential and natural origin, medicinal plants have been reported as the main source of natural antioxidants phytocompounds. Some non-enzymatic phytocompounds such as flavonoids, polyphenols, and glutathione, along with some vitamins have been reported to possess strong antioxidant activities in vivo and in vitro studies. Thus, the present review describes, in brief, the overview of oxidative stress-directed cellular damage and the unction of dietary antioxidants in the management of different diseases. The therapeutic limitations in correlating the antioxidant activity of foods to human health were also discussed.
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Affiliation(s)
- Priya Chaudhary
- Department of Bioscience and Biotechnology, Banasthali University Vanasthali, Rajasthan, India
| | - Pracheta Janmeda
- Department of Bioscience and Biotechnology, Banasthali University Vanasthali, Rajasthan, India
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Balakyz Yeskaliyeva
- Al-Farabi Kazakh National University, Faculty of Chemistry and Chemical Technology, Almaty, Kazakhstan
| | - Ahmad Faizal Abdull Razis
- Department of Food Science, Faculty of Food` Science and Technology, Universiti Putra Malaysia, Selangor, Malaysia
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia
| | - Babagana Modu
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia
- Department of Biochemistry, Faculty of Science, University of Maiduguri, Maiduguri, Nigeria
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania
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21
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Bardelčíková A, Šoltys J, Mojžiš J. Oxidative Stress, Inflammation and Colorectal Cancer: An Overview. Antioxidants (Basel) 2023; 12:antiox12040901. [PMID: 37107276 PMCID: PMC10135609 DOI: 10.3390/antiox12040901] [Citation(s) in RCA: 90] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/05/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Colorectal cancer (CRC) represents the second leading cause of cancer-related deaths worldwide. The pathogenesis of CRC is a complex multistep process. Among other factors, inflammation and oxidative stress (OS) have been reported to be involved in the initiation and development of CRC. Although OS plays a vital part in the life of all organisms, its long-term effects on the human body may be involved in the development of different chronic diseases, including cancer diseases. Chronic OS can lead to the oxidation of biomolecules (nucleic acids, lipids and proteins) or the activation of inflammatory signaling pathways, resulting in the activation of several transcription factors or the dysregulation of gene and protein expression followed by tumor initiation or cancer cell survival. In addition, it is well known that chronic intestinal diseases such as inflammatory bowel disease (IBD) are associated with an increased risk of cancer, and a link between OS and IBD initiation and progression has been reported. This review focuses on the role of oxidative stress as a causative agent of inflammation in colorectal cancer.
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Affiliation(s)
- Annamária Bardelčíková
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Tr. SNP 1, 040 11 Košice, Slovakia
| | - Jindřich Šoltys
- Institute of Parasitology, Slovak Academy of Science, Hlinkova 3, 040 01 Košice, Slovakia
| | - Ján Mojžiš
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Tr. SNP 1, 040 11 Košice, Slovakia
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22
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The Colorectal Cancer Microbiota Alter Their Transcriptome To Adapt to the Acidity, Reactive Oxygen Species, and Metabolite Availability of Gut Microenvironments. mSphere 2023; 8:e0062722. [PMID: 36847536 PMCID: PMC10117117 DOI: 10.1128/msphere.00627-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023] Open
Abstract
The gut microbiome is implicated in the pathology of colorectal cancer (CRC). However, the mechanisms by which the microbiota actively contribute to disease onset and progression remain elusive. In this pilot study, we sequenced fecal metatranscriptomes of 10 non-CRC and 10 CRC patient gut microbiomes and conducted differential gene expression analyses to assess any changed functionality in disease. We report that oxidative stress responses were the dominant activity across cohorts, an overlooked protective housekeeping role of the human gut microbiome. However, expression of hydrogen peroxide and nitric oxide-scavenging genes was diminished and augmented, respectively, positing that these regulated microbial responses have implications for CRC pathology. CRC microbes enhanced expression of genes for host colonization, biofilm formation, genetic exchange, virulence determinants, antibiotic, and acid resistances. Moreover, microbes promoted transcription of genes involved in metabolism of several beneficial metabolites, suggesting their contribution to patient metabolite deficiencies previously solely attributed to tumor cells. We showed in vitro that expression of genes involved in amino acid-dependent acid resistance mechanisms of meta-gut Escherichia coli responded differently to acid, salt, and oxidative pressures under aerobic conditions. These responses were mostly dictated by the host health status of origin of the microbiota, suggesting their exposure to fundamentally different gut conditions. These findings for the first time highlight mechanisms by which the gut microbiota can either protect against or drive colorectal cancer and provide insights into the cancerous gut environment that drives functional characteristics of the microbiome. IMPORTANCE The human gut microbiota has the genetic potential to drive colorectal cancer onset and progression; however, the expression of this genetic potential during the disease has not been investigated. We found that microbial expression of genes that detoxify DNA-damaging reactive oxygen species, which drive colorectal cancer, is compromised in cancer. We observed a greater activation of expression of genes involved in virulence, host colonization, exchange of genetic material, metabolite utilization, defense against antibiotics, and environmental pressures. Culturing gut Escherichia coli of cancerous and noncancerous metamicrobiota revealed different regulatory responses of amino acid-dependent acid resistance mechanisms in a health-dependent manner under environmental acid, oxidative, and osmotic pressures. Here, for the first time, we demonstrate that the activity of microbial genomes is regulated by the health status of the gut in vivo and in vitro and provides new insights for shifts in microbial gene expression in colorectal cancer.
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23
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Janion K, Strzelczyk JK, Walkiewicz KW, Biernacki K, Copija A, Szczepańska E, Nowakowska-Zajdel E. Evaluation of Malondialdehyde Level, Total Oxidant/Antioxidant Status and Oxidative Stress Index in Colorectal Cancer Patients. Metabolites 2022; 12:1118. [PMID: 36422258 PMCID: PMC9695970 DOI: 10.3390/metabo12111118] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/21/2022] [Accepted: 11/09/2022] [Indexed: 11/18/2022] Open
Abstract
Oxidative stress may play an important role in colorectal cancer (CRC). The present study included 94 adult patients with CRC (52 men and 42 women) and 26 hospitalized patients (12 men and 14 women) in whom CRC was excluded (control group). During hospitalization, blood serum samples were collected from both groups. Apart from that, anthropometric measurements were taken and other clinical data were analyzed. Serum malondialdehyde (MDA) level, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were assayed. Subsequently, the relationship between the analyzed oxidative stress markers and selected clinical characteristics was investigated in both groups. The evaluation of oxidative stress marker values demonstrated that MDA and TAS levels were significantly higher in the control group than the CRC group (p < 0.001 and p = 0.019, respectively), while TOS levels were significantly higher in the CRC group than the control group (p = 0.005). Significantly lower OSI levels were found in the control group than in the CRC group (p < 0.001). Similar results can be observed when performing ROC analysis (receiver operating characteristic curve). Preliminary statistical analysis demonstrated that MDA levels in the study group depend on the location of the primary tumour (p = 0.035). Based on the post hoc Tukey test, a relationship was demonstrated between the MDA level and the left and right side of the colon (p = 0.040). The results may be evidence for a higher level of oxidative stress, including a compromised antioxidative defence system, in patients with CRC.
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Affiliation(s)
- Karolina Janion
- Department of Nutrition-Related Disease Prevention, Department of Metabolic Disease Prevention, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Joanna Katarzyna Strzelczyk
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland
| | | | - Krzysztof Biernacki
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland
| | - Angelika Copija
- Department of Nutrition-Related Disease Prevention, Department of Metabolic Disease Prevention, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
- Department of Clinical Oncology, No. 4 Provincial Specialist Hospital in Bytom, 41-902 Bytom, Poland
| | - Elżbieta Szczepańska
- Department of Human Nutrition, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland
| | - Ewa Nowakowska-Zajdel
- Department of Nutrition-Related Disease Prevention, Department of Metabolic Disease Prevention, Faculty of Health Sciences in Bytom, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
- Department of Clinical Oncology, No. 4 Provincial Specialist Hospital in Bytom, 41-902 Bytom, Poland
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24
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Bioactive Compounds from Elderberry: Extraction, Health Benefits, and Food Applications. Processes (Basel) 2022. [DOI: 10.3390/pr10112288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Elderberries are appreciated for their antioxidant properties. Sambucus nigra L. is an extremely abundant plant in the wild flora of Romania, but it is underutilized. Elderberry is used in modern and traditional medicine due to the complex chemical composition of the fruit. The content of phenolic compounds is high (516–8974 mg/100 g DW), of which the most abundant are anthocyanins. Phenolic compounds are known for their beneficial effects on the body. Numerous studies have demonstrated the antioxidant capacity, antibacterial, antiviral, antidiabetic, and anticancer properties of the fruit. It is considered that most of the therapeutic properties of elderberries can be correlated with the antioxidant activity they have. S. nigra fruits are also used in the food industry. Some studies have shown that the therapeutic properties of elderberries can also be found in the products obtained from them. Therefore, this review aimed to describe the chemical composition of elderberries and products obtained from them, the positive effects on the body, and the methods by which the bioactive compounds can be extracted from the fruits and analyzed. This manuscript is useful for extraction optimization and characterization in order to valorize new functional foods, food supplements, and also in new pharmaceutical products.
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25
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Fathi S, Ahmadzadeh M, Vahdat M, Afsharfar M, Roumi Z, Hassanpour Ardekanizadeh N, Shekari S, Poorhosseini SM, Gholamalizadeh M, Abdollahi S, Kheyrani E, Doaei S. The effect of FTO rs9939609 polymorphism on the association between colorectal cancer and dietary fiber. Front Nutr 2022; 9:891819. [PMID: 36263301 PMCID: PMC9576139 DOI: 10.3389/fnut.2022.891819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 09/07/2022] [Indexed: 11/13/2022] Open
Abstract
Background Gene polymorphisms may explain the controversy on the association between colorectal cancer (CRC) and dietary fibers. The purpose of this study was to investigate the effect of fat mass and obesity-associated (FTO) rs9939609 polymorphism on the association between colorectal cancer and dietary fiber. Methods This case-control study was conducted on 160 CRC cases and 320 healthy controls in Tehran, Iran. The participants' food intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). The frequency of rs9939609 FTO polymorphism in the case and control groups was determined using the tetra-primer amplification refractory mutation (tetra-ARMS) method. Results In the participants with the TT genotype of the FTO rs9939609, the cases had higher BMI and lower intake of dietary fiber compared to the controls (P = 0.01). Among A allele carriers of FTO rs9939609 polymorphism, the cases had higher BMI (P = 0.04) and lower intake of total fiber (P = 0.02) and soluble fiber (P = 0.02). An inverse association was found between CRC and dietary fiber intake among those with the AA/AT FTO rs9939609 genotype after adjusting for age, sex, smoking, alcohol consumption, physical activity, BMI, and calorie intake (OR = 0.9, CI 95%:0.84-0.92, P < 0.05). Conclusion This study found a link between higher dietary fiber consumption and a lower risk of CRC in A-allele carriers of FTO rs9939609 polymorphism. Future studies are needed to identify the underlying mechanisms of the association between CRC and dietary fibers in people with different FTO genotypes.
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Affiliation(s)
- Soroor Fathi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Ahmadzadeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Vahdat
- Aboozar Children's Medical Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Afsharfar
- Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Zahra Roumi
- Master of Science Student of Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Soheila Shekari
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Seyed Mohammad Poorhosseini
- Genomic Research Center, Department of Medical Genetic, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Gholamalizadeh
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Abdollahi
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Kheyrani
- Taban Medical Genetic Laboratory, Tehran, Iran,Research Center of Health and Environment, School of Health, Guilan University of Medical Sciences, Rasht, Iran
| | - Saeid Doaei
- Department of Community Nutrition, School of Nutrition and Food Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran,*Correspondence: Saeid Doaei
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26
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Okagu IU, Udenigwe CC. Transepithelial transport and cellular mechanisms of food-derived antioxidant peptides. Heliyon 2022; 8:e10861. [PMID: 36217466 PMCID: PMC9547200 DOI: 10.1016/j.heliyon.2022.e10861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 04/23/2022] [Accepted: 09/27/2022] [Indexed: 11/18/2022] Open
Abstract
Considering the involvement of oxidative stress in the etiology of many non-communicable diseases, food-derived antioxidant peptides (FDAPs) are strong candidates for nutraceutical development for disease prevention and management. This paper reviews current evidence on the transepithelial transport and cellular mechanisms of antioxidant activities of FDAPs. Several FDAPs have multiple health benefits such as anti-inflammatory and anti-photoaging activities, in addition to antioxidant properties through which they protect cellular components from oxidative damage. Some FDAPs have been shown to permeate the intestinal epithelium, which could facilitate their bioavailability and physiological bioactivities. Molecular mechanisms of FDAPs include suppression of oxidative stress as evidenced by reduction in intracellular reactive oxygen species production, lipid peroxidation and apoptotic protein activation as well as increase in antioxidant defense mechanisms (enzymatic and non-enzymatic). Since many FDAPs have demonstrated promising antioxidant activity, future investigation should focus on further elucidation of molecular mechanisms and human studies to explore their practical application for the prevention and management of oxidative stress-related diseases.
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Affiliation(s)
- Innocent U. Okagu
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - Chibuike C. Udenigwe
- School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada
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27
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Oxidative Stress and DNA Damage Markers in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms231911664. [PMID: 36232966 PMCID: PMC9569897 DOI: 10.3390/ijms231911664] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 09/27/2022] [Accepted: 09/29/2022] [Indexed: 11/05/2022] Open
Abstract
Oxidative stress (OS) and inflammation are known to play an important role in chronic diseases, including cancer, and specifically colorectal cancer (CRC). The main objective of this study was to explore the diagnostic potential of OS markers in patients with CRC, which may translate into an early diagnosis of the disease. To do this, we compared results with those in a group of healthy controls and assessed whether there were significant differences. In addition, we explored possible correlations with the presence of tumors and tumor stage, with anemia and with inflammatory markers used in clinical practice. The study included 80 patients with CRC and 60 healthy controls. The following OS markers were analyzed: catalase (CAT), reduced glutathione (GSH) and oxidized glutathione (GSSG) in serum; and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and F2-isoprotanes in urine (F2-IsoPs). Tumor markers (CEA and CA 19.9), anemia markers (hemoglobin, hematocrit and medium corpuscular volume) and inflammatory markers (leukocytes, neutrophils, N/L index, platelets, fibrinogen, C-reactive protein, CRP and IL-6) were also determined. Comparison of means between patients and controls revealed highly significant differences for all OS markers, with an increase in the prooxidant markers GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and a decrease in the antioxidant markers CAT and GSH. Tumor and inflammatory markers (except CRP) correlated positively with GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and negatively with CAT and GSH. In view of the results obtained, OS markers may constitute a useful tool for the early diagnosis of CRC patients.
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28
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Chiang FF, Chao TH, Huang SC, Cheng CH, Tseng YY, Huang YC. Cysteine Regulates Oxidative Stress and Glutathione-Related Antioxidative Capacity before and after Colorectal Tumor Resection. Int J Mol Sci 2022; 23:ijms23179581. [PMID: 36076975 PMCID: PMC9455234 DOI: 10.3390/ijms23179581] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Abstract
Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.
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Affiliation(s)
- Feng-Fan Chiang
- Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- Department of Food and Nutrition, Providence University, Taichung 43301, Taiwan
| | - Te-Hsin Chao
- Chiayi & Wanqiao Branch, Taichung Veterans General Hospital, Chiayi 60090, Taiwan
| | - Shih-Chien Huang
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Department of Health Industry Technology Management, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Chien-Hsiang Cheng
- Department of Respiratory Therapy, Taichung Veterans General Hospital, Taichung 40705, Taiwan
| | - Yu-Yao Tseng
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Yi-Chia Huang
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Correspondence:
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29
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Amirsasan R, Akbarzadeh M, Akbarzadeh S. Exercise and colorectal cancer: prevention and molecular mechanisms. Cancer Cell Int 2022; 22:247. [PMID: 35945569 PMCID: PMC9361674 DOI: 10.1186/s12935-022-02670-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 08/02/2022] [Indexed: 12/16/2022] Open
Abstract
Exercise and physical activity have been shown to be strongly associated with a decreased incidence rate of various chronic diseases especially numerous human malignancies. A huge number of clinical trials and meta-analysis have demonstrated that exercise is significantly effective in lowering the risk of colorectal cancer. In addition, it is suggested as an effective therapeutic modality against this cancer type. Therefore, in this review, we will review comprehensibly the effects of exercise in preventing, treating, and alleviating the adverse effects of conventional therapeutic options in colorectal cancer. Moreover, the possible mechanisms underlying the positive effects of exercise and physical activity in colorectal cancer, including regulation of inflammation, apoptosis, growth factor axis, immunity, epigenetic, etc. will be also discussed.
Exercise is an effective post-treatment management program in colorectal cancer survivals Exercise improves muscle strength, cardiorespiratory fitness, emotional distress, physical activity, fatigue, and sleep quality in colorectal patients undergoing chemotherapy Targeting and modulating insulin-like growth factor (IGF) system, inflammation, apoptosis, immunity, epigenetic, Leptin and Ghrelin, and signaling pathways are major underlying mechanisms for preventive effects of exercise in colorectal cancer
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Affiliation(s)
- Ramin Amirsasan
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran
| | - Maryam Akbarzadeh
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Shabnam Akbarzadeh
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran.
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30
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Quantitative proteomics to study aging in rabbit spleen tissues. Exp Gerontol 2022; 167:111908. [PMID: 35932934 DOI: 10.1016/j.exger.2022.111908] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/25/2022] [Accepted: 07/27/2022] [Indexed: 11/04/2022]
Abstract
Aging is a process that occurs in tissues and across species, leading to the degradation of many biological processes. We previously demonstrated that rabbits are a feasible model for studying aging due to their genetic homology and relatively short lifespan in comparison to humans. We utilized a cPILOT multiplexing strategy to identify proteomic changes in spleen tissues of young, middle, and old aged rabbits. We identified 63 proteins that change significantly (p < 0.05) with age and notably these proteins relate to nucleotide and RNA binding, DNA repair, actin regulation, and immune system pathways. Here, we explore the implications of aging in the spleen and demonstrate the utility of a rabbit model to understand aging processes.
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Cacciola NA, Salzano A, D’Onofrio N, Venneri T, Cicco PD, Vinale F, Petillo O, Martano M, Maiolino P, Neglia G, Campanile C, Severino L, Merola C, Borrelli F, Balestrieri ML, Campanile G. Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer. Int J Mol Sci 2022; 23:8464. [PMID: 35955595 PMCID: PMC9368892 DOI: 10.3390/ijms23158464] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/24/2022] [Accepted: 07/27/2022] [Indexed: 02/01/2023] Open
Abstract
Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.
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Affiliation(s)
- Nunzio Antonio Cacciola
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
- Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino 111, 80131 Naples, Italy;
| | - Angela Salzano
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
| | - Nunzia D’Onofrio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (N.D.); (M.L.B.)
| | - Tommaso Venneri
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy;
| | - Paola De Cicco
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy;
| | - Francesco Vinale
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
| | - Orsolina Petillo
- Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino 111, 80131 Naples, Italy;
| | - Manuela Martano
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
| | - Paola Maiolino
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
| | - Gianluca Neglia
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
| | - Ciro Campanile
- Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, Consiglio Nazionale delle Ricerche (CNR), 80131 Naples, Italy;
| | - Lorella Severino
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
| | - Carmine Merola
- Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Balzarini 1, 64100 Teramo, Italy;
| | - Francesca Borrelli
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy;
| | - Maria Luisa Balestrieri
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (N.D.); (M.L.B.)
| | - Giuseppe Campanile
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy; (N.A.C.); (A.S.); (P.D.C.); (F.V.); (M.M.); (P.M.); (G.N.); (L.S.); (G.C.)
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Wu F, Ma H, Wang X, Wei H, Zhang W, Zhang Y. The histidine phosphatase LHPP: an emerging player in cancer. Cell Cycle 2022; 21:1140-1152. [PMID: 35239447 PMCID: PMC9103355 DOI: 10.1080/15384101.2022.2044148] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Cancers continue to have high incidence and mortality rates worldwide. Therefore, cancer control remains the main public health goal. Growing research evidence suggests that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) plays an important role in inhibiting tumor cell progression. It has been reported in the literature that LHPP is expressed at low levels in tumor tissues and cells and that patients with low LHPP expression have a poorer prognosis. Functional studies have shown that LHPP can inhibit tumor cell proliferation, metastasis, and apoptosis by affecting different target genes. In addition, researchers have used iDPP nanoparticles to deliver LHPP plasmids to treat tumors, demonstrating the great potential of LHPP plasmids for cancer therapy. In our review, we highlight the biological functions and important downstream target genes of LHPP in tumors, providing a theoretical basis for the treatment of human cancers. Although not thoroughly studied in terms of tumor mechanisms, LHPP still represents a promising and effective anticancer drug target.
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Affiliation(s)
- Fahong Wu
- Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Hanwei Ma
- Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Xiaoli Wang
- Department of Gynaecology and Obstetrics, The Third Hospital of Xiamen, Xiamen, China
| | - Hangzhi Wei
- Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Wei Zhang
- Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Youcheng Zhang
- Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, Gansu, China,CONTACT Youcheng Zhang Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, 730030Gansu, China
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Aksoy AS, Arici M, Yaman M. The effect of hardaliye on reducing the formation of malondialdehyde during in vitro gastrointestinal digestion of meat products. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Venturelli S, Leischner C, Helling T, Renner O, Burkard M, Marongiu L. Minerals and Cancer: Overview of the Possible Diagnostic Value. Cancers (Basel) 2022; 14:1256. [PMID: 35267564 PMCID: PMC8909570 DOI: 10.3390/cancers14051256] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 02/23/2022] [Accepted: 02/26/2022] [Indexed: 12/16/2022] Open
Abstract
Cancer is the second leading cause of death worldwide and is expected to increase by one-third over the next two decades, in parallel with the growing proportion of the elderly population. Treatment and control of cancer incidence is a global issue. Since there is no clear way to prevent or cure this deadly malignancy, diagnostic, predictive, and prognostic markers for oncological diseases are of great therapeutic value. Minerals and trace elements are important micronutrients for normal physiological function of the body. They are abundant in natural food sources and are regularly included in dietary supplements whereas highly processed industrial food often contains reduced or altered amounts of them. In modern society, the daily intake, storage pools, and homeostasis of these micronutrients are dependent on certain dietary habits and can be thrown out of balance by malignancies. The current work summarizes the data on minerals and trace elements associated with abnormal accumulation or depletion states in tumor patients and discusses their value as potential tumor-associated biomarkers that could be introduced into cancer therapy.
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Affiliation(s)
- Sascha Venturelli
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany; (S.V.); (C.L.); (T.H.); (O.R.)
- Department of Vegetative and Clinical Physiology, Institute of Physiology, University of Tuebingen, Wilhelmstraße 56, 72074 Tuebingen, Germany
| | - Christian Leischner
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany; (S.V.); (C.L.); (T.H.); (O.R.)
| | - Thomas Helling
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany; (S.V.); (C.L.); (T.H.); (O.R.)
| | - Olga Renner
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany; (S.V.); (C.L.); (T.H.); (O.R.)
| | - Markus Burkard
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany; (S.V.); (C.L.); (T.H.); (O.R.)
| | - Luigi Marongiu
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany; (S.V.); (C.L.); (T.H.); (O.R.)
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Jangde S, Purohit MR, Saraf F, Merchant N, Bhaskar LVKS. Dietary Phytocompounds for Colon Cancer Therapy. ONCO THERAPEUTICS 2022; 9:69-82. [DOI: 10.1615/oncotherap.2022046215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2025]
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Andrabi Q, Ramalingam S. Role of Notch Signalling in Oxidative Stress and Stem Cell Self-Renewal During Colitis and Colon Cancer. HANDBOOK OF OXIDATIVE STRESS IN CANCER: THERAPEUTIC ASPECTS 2022:1623-1637. [DOI: 10.1007/978-981-16-5422-0_82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Kachur O, Fira L, Lykhatskyі P, Fira D, Stechyshyn I. The state of pro- and antioxidant systems in rats with DMH-induced colon carcinogenesis on the background of extracorporeal detoxification. PHARMACIA 2021. [DOI: 10.3897/pharmacia.68.e71840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Aim: Cancer is one of the leading causes of death in the world. The aim of this research was to study the indices of pro- and antioxidant systems in rats with dimethylhydrazine (DMH)-induced colon carcinogenesis on the background of the enterosorbent AUT-M use.
Materials and methods: The study was performed on 70 white male rats weighing 200–250 g. Adenocarcinoma of the colon was simulated by subcutaneous injection of the DMH (Sigma-Aldrich Chemie, Japan) at a dose of 7.2 mg/kg once a week during 7 months. Enterosorbent AUT-M was administered intragastrically daily for 21 days after simulation of carcinogenesis at a dose of 1 ml of suspension per 100 g of animal body weight. The state of the pro- and antioxidant systems was studied by the content of oxidative modification of proteins products (OMP), the activity of superoxide dismutase (SOD), catalase (CAT), contents of ceruloplasmin (CP) and reduced glutathione (GSH).
Results: It was found that DMH-induced colon carcinogenesis in rats is accompanied by disorders in the antioxidant defense system and activation of free radical oxidation processes. Enterosorbent AUT-M provides a significant reduction in the content of OMP370 and OMP430 in both blood serum and liver homogenate of rats. Moreover, the use of enterosorbent AUT-M demonstrated a significant increase in the activity of SOD, CAT, content of GSH and a decrease in CP content in investigated tissues.
Conclusion: The use of enterosorbent AUT-М demonstrated prominent potential suppression for oxidative stress and positive effect on antioxidant defense system in rats with DMH-induced colon carcinogenesis.
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Rasool M, Malik A, Waquar S, Ain QT, Rasool R, Asif M, Anfinan N, Haque A, Alam H, Ahmed S, Hamid Hamdard M. Assessment of clinical variables as predictive markers in the development and progression of colorectal cancer. Bioengineered 2021; 12:2288-2298. [PMID: 34096454 PMCID: PMC8806642 DOI: 10.1080/21655979.2021.1933680] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is graded as one of the most common cancer. It accounts for the second leading cause of cancer deaths worldwide. The present study intends to investigate the role and importance of different biochemical variables in the development of colorectal cancer.In this cross-sectional study we recruited ninety-one patients diagnosed with colorectal cancer and fifty-three age-sex matched controls from June 2017 to June 2018. Different variables i.e. SOD, GSH, CAT, MDA, TGF, VEGF, TNF, ILs, MMPs, etc., were estimated with the help of their respective methods. Our findings suggest a significant increase in the levels of different inflammatory and stress-related markers. The NFκB, TGF-β, VEGFβ, 8OHdG, IsoP-2α were significantly found to be increased in patients with colon cancer (0.945 ± 0.067 μg/ml, 18.59 ± 1.53 pg/ml, 99.35 ± 4.29 pg/ml, 21.26 ± 1.29 pg/ml, 102.25 ± 4.25 pg/ml) as compared to controls (0.124 ± 0.024 μg/ml, 8.26 ± 0.88 pg/ml, 49.58 ± 2.62 pg/ml, 0.93 ± 0.29 pg/ml, 19.65 ± 3.19 pg/ml). Notably, the levels of different antioxidants were shown to be significantly lower in patients of colon cancer. The present study concluded that excessive oxidative stress and lipid peroxidation result in a decrease in the antioxidative capacity of cells which may influence diverse signaling cascades including NF-KB, which results in DNA modification and gene transcription that ultimately involved in the progression of colon cancer.
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Affiliation(s)
- Mahmood Rasool
- Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Arif Malik
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Sulayman Waquar
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Qura Tul Ain
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Rabia Rasool
- Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan
| | - Muhammad Asif
- Department of Biotechnology, BUITEMS, Quetta, Pakistan
- ORIC, Buitems, Quetta, Pakistan
| | - Nisreen Anfinan
- Gynecology Oncology Unit, Obstetrics and Gynaecology Department, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Absarul Haque
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hina Alam
- Pakistan Institute of Medical Sciences, Islamabad, Pakistan
| | - Sagheer Ahmed
- Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University Islamabad
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Wang T, Wang P, Ge W, Shi C, Xiao G, Wang X, Lü X. Protective effect of a multi-strain probiotics mixture on azoxymethane/dextran sulfate sodium-induced colon carcinogenesis. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101346] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Sherif DA, Makled MN, Suddek GM. The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD-induced colorectal cancer in Wistar rats. Fundam Clin Pharmacol 2021; 35:940-954. [PMID: 33829539 DOI: 10.1111/fcp.12679] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/29/2021] [Accepted: 04/06/2021] [Indexed: 12/30/2022]
Abstract
Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50 mg/kg (i.p.) for 24 weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group. Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50 mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.
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Affiliation(s)
- Dana A Sherif
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.,Clinical Pharmacy Department, Gastrointestinal Surgery Center (GISC), Mansoura University, Mansoura, Egypt
| | - Mirhan N Makled
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Ghada M Suddek
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Catalano T, D’Amico E, Moscatello C, Di Marcantonio MC, Ferrone A, Bologna G, Selvaggi F, Lanuti P, Cotellese R, Curia MC, Lattanzio R, Aceto GM. Oxidative Distress Induces Wnt/β-Catenin Pathway Modulation in Colorectal Cancer Cells: Perspectives on APC Retained Functions. Cancers (Basel) 2021; 13:6045. [PMID: 34885156 PMCID: PMC8656656 DOI: 10.3390/cancers13236045] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/25/2021] [Accepted: 11/27/2021] [Indexed: 01/10/2023] Open
Abstract
Colorectal cancer (CRC) is a multistep process that arises in the colic tissue microenvironment. Oxidative stress plays a role in mediating CRC cell survival and progression, as well as promoting resistance to therapies. CRC progression is associated with Wnt/β-Catenin signaling dysregulation and loss of proper APC functions. Cancer recurrence/relapse has been attributed to altered ROS levels, produced in a cancerous microenvironment. The effect of oxidative distress on Wnt/β-Catenin signaling in the light of APC functions is unclear. This study evaluated the effect of H2O2-induced short-term oxidative stress in HCT116, SW480 and SW620 cells with different phenotypes of APC and β-Catenin. The modulation and relationship of APC with characteristic molecules of Wnt/β-Catenin were assessed in gene and protein expression. Results indicated that CRC cells, even when deprived of growth factors, under acute oxidative distress conditions by H2O2 promote β-Catenin expression and modulate cytoplasmic APC protein. Furthermore, H2O2 induces differential gene expression depending on the cellular phenotype and leading to favor both Wnt/Catenin-dependent and -independent signaling. The exact mechanism by which oxidative distress can affect Wnt signaling functions will require further investigation to reveal new scenarios for the development of therapeutic approaches for CRC, in the light of the conserved functions of APC.
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Affiliation(s)
- Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;
| | - Emira D’Amico
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (E.D.); (C.M.); (F.S.); (R.C.); (M.C.C.)
| | - Carmelo Moscatello
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (E.D.); (C.M.); (F.S.); (R.C.); (M.C.C.)
| | - Maria Carmela Di Marcantonio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (M.C.D.M.); (R.L.)
| | - Alessio Ferrone
- Department of Medicine and Aging Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (A.F.); (G.B.); (P.L.)
| | - Giuseppina Bologna
- Department of Medicine and Aging Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (A.F.); (G.B.); (P.L.)
- Center for Advanced Studies and Technology (C.A.S.T.), University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
| | - Federico Selvaggi
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (E.D.); (C.M.); (F.S.); (R.C.); (M.C.C.)
- Unit of General Surgery, Ospedale Floraspe Renzetti, Lanciano, 66034 Chieti, Italy
| | - Paola Lanuti
- Department of Medicine and Aging Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (A.F.); (G.B.); (P.L.)
- Center for Advanced Studies and Technology (C.A.S.T.), University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
| | - Roberto Cotellese
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (E.D.); (C.M.); (F.S.); (R.C.); (M.C.C.)
- Villa Serena Foundation for Research, Via Leonardo Petruzzi, 65013 Città Sant’Angelo, Italy
| | - Maria Cristina Curia
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (E.D.); (C.M.); (F.S.); (R.C.); (M.C.C.)
| | - Rossano Lattanzio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (M.C.D.M.); (R.L.)
- Center for Advanced Studies and Technology (C.A.S.T.), University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
| | - Gitana Maria Aceto
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy; (E.D.); (C.M.); (F.S.); (R.C.); (M.C.C.)
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Lukasheva EV, Babayeva G, Karshieva SS, Zhdanov DD, Pokrovsky VS. L-Lysine α-Oxidase: Enzyme with Anticancer Properties. Pharmaceuticals (Basel) 2021; 14:1070. [PMID: 34832852 PMCID: PMC8618108 DOI: 10.3390/ph14111070] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/19/2021] [Accepted: 10/20/2021] [Indexed: 11/19/2022] Open
Abstract
L-lysine α-oxidase (LO), one of L-amino acid oxidases, deaminates L-lysine with the yield of H2O2, ammonia, and α-keto-ε-aminocaproate. Multiple in vitro and in vivo studies have reported cytotoxic, antitumor, antimetastatic, and antitumor activity of LO. Unlike asparaginase, LO has a dual mechanism of action: depletion of L-lysine and formation of H2O2, both targeting tumor growth. Prominent results were obtained on murine and human tumor models, including human colon cancer xenografts HCT 116, LS174T, and T47D with maximum T/C 12, 37, and 36%, respectively. The data obtained from human cancer xenografts in immunodeficient mice confirm the potential of LO as an agent for colon cancer treatment. In this review, we discuss recently discovered molecular mechanisms of biological action and the potential of LO as anticancer enzyme.
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Affiliation(s)
- Elena V. Lukasheva
- Department of Biochemistry, Peoples’ Friendship University of Russia (RUDN University), Miklukho—Maklaya Street 6, 117198 Moscow, Russia; (E.V.L.); (G.B.)
| | - Gulalek Babayeva
- Department of Biochemistry, Peoples’ Friendship University of Russia (RUDN University), Miklukho—Maklaya Street 6, 117198 Moscow, Russia; (E.V.L.); (G.B.)
- Laboratory of Combined Treatment, N.N. Blokhin Cancer Research Center, Kashirskoe Shosse 24, 115478 Moscow, Russia;
| | - Saida Sh. Karshieva
- Laboratory of Combined Treatment, N.N. Blokhin Cancer Research Center, Kashirskoe Shosse 24, 115478 Moscow, Russia;
| | - Dmitry D. Zhdanov
- Institute of Biomedical Chemistry, Pogodinskaya Street 10/8, 119121 Moscow, Russia;
| | - Vadim S. Pokrovsky
- Department of Biochemistry, Peoples’ Friendship University of Russia (RUDN University), Miklukho—Maklaya Street 6, 117198 Moscow, Russia; (E.V.L.); (G.B.)
- Laboratory of Combined Treatment, N.N. Blokhin Cancer Research Center, Kashirskoe Shosse 24, 115478 Moscow, Russia;
- Center of Genetics and Life Sciences, Sirius University of Science and Technology, Federal Territory Sirius, 1 Olimpiisky Prospect, 354340 Sochi, Russia
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Alkadhim Naji BA, Thamir Mahdi W. CYP2E1 Polymorphisms and Colorectal Cancer. RESEARCH JOURNAL OF PHARMACY AND TECHNOLOGY 2021:3879-3882. [DOI: 10.52711/0974-360x.2021.00673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Background: The hepatic cytochrome P450 2E1 (CYP2E1) enzyme plays an important role in the metabolic activation of nitrosamines and other carcinogenic compounds. Aim of the study: To determine the effect of chemotherapy and radiation for colorectal cancer patients on some biochemical and molecular parameters. Patients and methods: The current study was conducted in the Department of Biology at the College of Science at the University of Al-Qadisiyah and in cooperation with the Cancer Center in the Najaf city and the Department of Medicine City in Baghdad, Iraq during the period from November 15, 2019, to May 6, 2020. The study group included a total of (90) samples were taken from males and females of ages ranged between (33 years to 80 years) and then it was divided into two groups. The first included (60) samples of people with colorectal cancer (CRC), and the second included (30) samples of people The healthy ones represented the control group. (5ml) of venous blood was withdrawn and the sample was divided into two groups, the first was placed in tubes containing an anti-clotting substance for molecular examination and kept at a temperature (-20) until use, and the other part was placed in Gel tube tubes and then placed in a centrifuge to separate Serum, for the purpose of biochemical examinations. With regard to the results of the values of oxidative stress indicators (SOD, GSH, MDA). Results: there was a significant difference in the level of (SOD, GSH) between the control and treatment groups, where the highest percentage was in the control group, followed by the radiotherapy group and then chemotherapy. The results showed a significant increase in the MDA value of the chemotherapy group compared with the radiotherapy and control group. The results of the molecular study to study the genotypes of the CYPIE2 gene showed that the C1/C1 type is the normal type for the CYPIE2 gene and that the ratio of this type did not show any significant difference between the groups, while the C2/C2 type showed no significant difference between the groups and the C2/C2 type. Conclusion: It can be concluded that the use of radiotherapy and chemotherapy to treat patients with CRC cancer has a clear effect on health and on many of the patient's physiological and biochemical indicators, and this, in turn, is reflected in the patient's ability to fight the disease.
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Acevedo-León D, Monzó-Beltrán L, Gómez-Abril SÁ, Estañ-Capell N, Camarasa-Lillo N, Pérez-Ebri ML, Escandón-Álvarez J, Alonso-Iglesias E, Santaolaria-Ayora ML, Carbonell-Moncho A, Ventura-Gayete J, Pla L, Martínez-Bisbal MC, Martínez-Máñez R, Bagán-Debón L, Viña-Almunia A, Martínez-Santamaría MA, Ruiz-Luque M, Alonso-Fernández J, Bañuls C, Sáez G. The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer. Int J Mol Sci 2021; 22:ijms22126183. [PMID: 34201191 PMCID: PMC8226858 DOI: 10.3390/ijms22126183] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/27/2021] [Accepted: 06/02/2021] [Indexed: 12/13/2022] Open
Abstract
The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.
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Affiliation(s)
- Delia Acevedo-León
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Lidia Monzó-Beltrán
- Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Odontotología-INCLIVA, Universidad de Valencia, 46010 Valencia, Spain; (L.M.-B.); (E.A.-I.)
| | - Segundo Ángel Gómez-Abril
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain;
| | - Nuria Estañ-Capell
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Natalia Camarasa-Lillo
- Servicio de Anatomía Patológica, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (N.C.-L.); (M.L.P.-E.); (J.E.-Á.)
| | - Marisa Luisa Pérez-Ebri
- Servicio de Anatomía Patológica, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (N.C.-L.); (M.L.P.-E.); (J.E.-Á.)
| | - Jorge Escandón-Álvarez
- Servicio de Anatomía Patológica, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (N.C.-L.); (M.L.P.-E.); (J.E.-Á.)
| | - Eulalia Alonso-Iglesias
- Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Odontotología-INCLIVA, Universidad de Valencia, 46010 Valencia, Spain; (L.M.-B.); (E.A.-I.)
| | - Marisa Luisa Santaolaria-Ayora
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Araceli Carbonell-Moncho
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Josep Ventura-Gayete
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Luis Pla
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València—Universitat de València, 46022 Valencia, Spain; (L.P.); (M.C.M.-B.); (R.M.-M.)
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
| | - Maria Carmen Martínez-Bisbal
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València—Universitat de València, 46022 Valencia, Spain; (L.P.); (M.C.M.-B.); (R.M.-M.)
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
- Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
- Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València—Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain
- Departamento de Química, Universitat Politècnica de València, 46022 Valencia, Spain
- Departamento de Química Física, Universitat de València, Burjasot, 46100 Valencia, Spain
| | - Ramón Martínez-Máñez
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València—Universitat de València, 46022 Valencia, Spain; (L.P.); (M.C.M.-B.); (R.M.-M.)
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
- Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
- Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València—Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain
- Departamento de Química, Universitat Politècnica de València, 46022 Valencia, Spain
- Departamento de Química Física, Universitat de València, Burjasot, 46100 Valencia, Spain
| | - Leticia Bagán-Debón
- Departamento de Estomatología, Facultad de Medicina y Odontología-INCLIVA, 46010 Valencia, Spain;
| | - Aurora Viña-Almunia
- Centro de Salud San Isidro, Consorcio Hospital General Universitario de Valencia, 46014 Valencia, Spain;
| | - M. Amparo Martínez-Santamaría
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - María Ruiz-Luque
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Jorge Alonso-Fernández
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
| | - Celia Bañuls
- Servicio de Endocrinología y Nutrición, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain
- Correspondence: (C.B.); (G.S.); Tel.: +34-96-318-9132 (C.B.); +34-96-386-4160 (G.S.)
| | - Guillermo Sáez
- Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain; (D.A.-L.); (N.E.-C.); (M.L.S.-A.); (A.C.-M.); (J.V.-G.); (M.A.M.-S.); (M.R.-L.); (J.A.-F.)
- Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Odontotología-INCLIVA, Universidad de Valencia, 46010 Valencia, Spain; (L.M.-B.); (E.A.-I.)
- Correspondence: (C.B.); (G.S.); Tel.: +34-96-318-9132 (C.B.); +34-96-386-4160 (G.S.)
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Xia X, Zhang X, Liu M, Duan M, Zhang S, Wei X, Liu X. Toward improved human health: efficacy of dietary selenium on immunity at the cellular level. Food Funct 2021; 12:976-989. [PMID: 33443499 DOI: 10.1039/d0fo03067h] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Selenium, an essential trace element in the body, participates in various biological processes in the form of selenoproteins. In humans, a suitable concentration of selenium is essential for maintaining normal cellular function. Decreased levels of selenoproteins can lead to obstruction of the normal physiological functions of tissues and cells and even death. In addition, the level of selenium in the body affects cellular immunity, humoral immunity, and the balance between type 2 and type 1 helper T cells. Selenium can affect the immune function of the body through the reactive oxygen species (ROS), NF-κB, ferroptosis and NRF2 pathways. This paper reviews the immune effect of selenium on the body and the process of signal transduction and aims to serve as a reference for follow-up studies of immune function and research on the development of new selenium compounds and active targets.
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Affiliation(s)
- Xiaojing Xia
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, Henan, PR China.
| | - Xiulin Zhang
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, Shanxi, PR China
| | - Mingcheng Liu
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, Henan, PR China.
| | - Mingyuan Duan
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, Henan, PR China.
| | - Shanshan Zhang
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, Henan, PR China.
| | - Xiaobing Wei
- College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, Henan, PR China.
| | - Xingyou Liu
- Xinxiang University, Xinxiang 453003, Henan, PR China.
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Gamage SMK, Lee KTW, Dissabandara DLO, Lam AKY, Gopalan V. Dual role of heme iron in cancer; promotor of carcinogenesis and an inducer of tumour suppression. Exp Mol Pathol 2021; 120:104642. [PMID: 33905708 DOI: 10.1016/j.yexmp.2021.104642] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/14/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE Heme is a crucial compound for cell survival but is also equipped with the potential to be toxic and carcinogenic to cells. However, with the recent advancement of knowledge regarding ferroptosis, the iron mediated cell death, heme can be postulated to induce tumour suppression through ferroptosis. This review summarizes the literature on the carcinogenic and anticarcinogenic properties of heme with specific emphasis on the alterations observed on heme synthesis, metabolism and transport in tumour cells. METHODS Literature search was performed in PubMed data base using the MeSH terms 'heme iron or heme', 'cancer or carcinogenesis' and 'tumour suppression' or 'anticarcinogenic properties. Out of 189 results, 166 were relevant to the current review. RESULTS Heme supports carcinogenesis via modulation of immune cell function, promoting inflammation and gut dysbiosis, impeding tumour suppressive potential of P53 gene, promoting cellular cytotoxicity and reactive oxygen species generation and modulating Nfr2 /HO-1 axis. The carcinogenic and anticarcinogenic properties of heme are both dose and oxygen concentration dependant. At low doses, heme is harmless and even helpful in maintaining the much-needed redox balance within the cell. However, when heme exceeds physiological concentrations, it could initiate and propagate carcinogenesis, due to its ability to produce reactive oxygen species (ROS). The same phenomenon of heme mediated ROS generation could be manipulated to initiate tumour suppression via ferroptosis, but the therapeutic doses are yet to be determined. CONCLUSION Heme iron possesses powerful carcinogenic and anticarcinogenic properties which are dosage and oxygen availability dependant.
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Affiliation(s)
- Sujani M K Gamage
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia; Department of Anatomy, Faculty of Medicine, University of Peradeniya, Sri Lanka
| | - Katherine T W Lee
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia
| | - D Lakal O Dissabandara
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia
| | - Alfred King-Yin Lam
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia.
| | - Vinod Gopalan
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia.
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Basnet U, Patil AR, Kulkarni A, Roy S. Role of Stress-Survival Pathways and Transcriptomic Alterations in Progression of Colorectal Cancer: A Health Disparities Perspective. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:5525. [PMID: 34063993 PMCID: PMC8196775 DOI: 10.3390/ijerph18115525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/07/2021] [Accepted: 05/19/2021] [Indexed: 12/09/2022]
Abstract
Every year, more than a million individuals are diagnosed with colorectal cancer (CRC) across the world. Certain lifestyle and genetic factors are known to drive the high incidence and mortality rates in some groups of individuals. The presence of enormous amounts of reactive oxygen species is implicated for the on-set and carcinogenesis, and oxidant scavengers are thought to be important in CRC therapy. In this review, we focus on the ethnicity-based CRC disparities in the U.S., the negative effects of oxidative stress and apoptosis, and gene regulation in CRC carcinogenesis. We also highlight the use of antioxidants for CRC treatment, along with screening for certain regulatory genetic elements and oxidative stress indicators as potential biomarkers to determine the CRC risk and progression.
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Affiliation(s)
- Urbashi Basnet
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA; (U.B.); (A.K.)
| | - Abhijeet R. Patil
- Computational Science Program, University of Texas at El Paso, El Paso, TX 79968, USA;
| | - Aditi Kulkarni
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA; (U.B.); (A.K.)
| | - Sourav Roy
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA; (U.B.); (A.K.)
- The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
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Lei L, Zhang J, Decker EA, Zhang G. Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer. Front Cell Dev Biol 2021; 9:665591. [PMID: 34079800 PMCID: PMC8165272 DOI: 10.3389/fcell.2021.665591] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 04/22/2021] [Indexed: 12/27/2022] Open
Abstract
Redox stress is a common feature of gut disorders such as colonic inflammation (inflammatory bowel disease or IBD) and colorectal cancer (CRC). This leads to increased colonic formation of lipid-derived electrophiles (LDEs) such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE). Recent research by us and others support that treatment with LDEs increases the severity of colitis and exacerbates the development of colon tumorigenesis in vitro and in vivo, supporting a critical role of these compounds in the pathogenesis of IBD and CRC. In this review, we will discuss the effects and mechanisms of LDEs on development of IBD and CRC and lifestyle factors, which could potentially affect tissue levels of LDEs to regulate IBD and CRC development.
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Affiliation(s)
- Lei Lei
- School of Medicine, Northwest University, Xi'an, China.,Department of Food Science, University of Massachusetts, Amherst, MA, United States
| | - Jianan Zhang
- Department of Food Science, University of Massachusetts, Amherst, MA, United States
| | - Eric A Decker
- Department of Food Science, University of Massachusetts, Amherst, MA, United States
| | - Guodong Zhang
- Department of Food Science, University of Massachusetts, Amherst, MA, United States.,Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, United States
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Abstract
Excessive gut luminal iron contributes to the initiation and progression of colorectal cancer. However, emerging evidence suggests that reduced iron intake and low systemic iron levels are also associated with the pathogenesis of colorectal cancer. This is important because patients with colorectal cancer often present with iron deficiency. Iron is necessary for appropriate immunological functions; hence, iron deficiency may hinder cancer immunosurveillance and potentially modify the tumor immune microenvironment, both of which may assist cancer development. This is supported by studies showing that patients with colorectal cancer with iron deficiency have inferior outcomes and reduced response to therapy. Here, we provide an overview of the immunological consequences of iron deficiency and suggest ensuring adequate iron therapy to limit these outcomes.
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Affiliation(s)
- Oliver Phipps
- O. Phipps, M.J. Brookes, and H.O. Al-Hassi are with the Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom
| | - Matthew J Brookes
- O. Phipps, M.J. Brookes, and H.O. Al-Hassi are with the Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom.,Royal Wolverhampton Hospitals NHS Trust, Gastroenterology Unit Wolverhampton, Wolverhampton, United Kingdom
| | - Hafid O Al-Hassi
- O. Phipps, M.J. Brookes, and H.O. Al-Hassi are with the Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom
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Afzal SM, Vafa A, Rashid S, Shree A, Islam J, Ali N, Sultana S. Amelioration of N,N'-dimethylhydrazine induced colon toxicity by epigallocatechin gallate in Wistar rats. Hum Exp Toxicol 2021; 40:1558-1571. [PMID: 33754881 DOI: 10.1177/09603271211002884] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Colon cancer is a life-threatening disease all over the world and is linked to constant oxidative stress and inflammation. Epigallocatechin gallate (EGCG), is a naturally occurring flavone possessing health benefiting pharmacological properties including antioxidant, anti-inflammatory and free radical scavenging properties. Our study investigates the role of EGCG on N,N'-dimethylhydrazine (DMH), a toxic environmental pollutant, induced colon toxicity. To investigate the effect of EGCG, Wistar rats were given EGCG for 7 days at the two doses of 10 and 20 mg/kg body weight and DMH was injected on the seventh day in all the group rats except the control. Our results indicate that DMH administration increased the oxidative stress (MDA) and depleted the glutathione and antioxidant enzyme activities (SOD, CAT, GR, GST and GPx) which was significantly ameliorated by EGCG treatment. Additionally DMH treatment upregulated inflammatory markers expression (NF-κB, COX-2 and IL-6) and enhanced mucosal damage in the colon. EGCG treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. We can conclude from the present study findings that EGCG protects the colon from DMH toxicity through its antioxidant and anti-inflammatory potential.
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Affiliation(s)
- S M Afzal
- Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, 28848Jamia Hamdard, New Delhi, India
| | - A Vafa
- Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, 28848Jamia Hamdard, New Delhi, India
| | - S Rashid
- Department of Pharmacology and Toxicology, College of Pharmacy, 204568Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - A Shree
- Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, 28848Jamia Hamdard, New Delhi, India
| | - J Islam
- Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, 28848Jamia Hamdard, New Delhi, India
| | - N Ali
- Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, 28848Jamia Hamdard, New Delhi, India.,Department of Pharmacology and Toxicology, College of Pharmacy, 37850King Saud University, Riyadh, Saudi Arabia
| | - S Sultana
- Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, 28848Jamia Hamdard, New Delhi, India
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