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Wu G, Ding Y, Li N, Zhang H, Liu N. Genome-Wide Identification of the Sulfate Transporter Gene Family Reveals That BolSULTR2;1 Regulates Plant Resistance to Alternaria brassicicola Through the Modulation of Glutathione Biosynthesis in Broccoli. Antioxidants (Basel) 2025; 14:496. [PMID: 40298881 PMCID: PMC12024372 DOI: 10.3390/antiox14040496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 04/16/2025] [Accepted: 04/16/2025] [Indexed: 04/30/2025] Open
Abstract
Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were identified from the Brassica genome. These BolSULTRs are distributed across nine chromosomes, with all collinear BolSULTR gene pairs undergoing purifying selections. Phylogenetic analysis reveals that the SULTR family is evolutionarily conserved among plant kingdoms. qRT-PCR analysis demonstrated that the expression of BolSULTRs varies across different plant organs and is modulated by hormonal signals. Furthermore, transcriptome analysis identified several BolSULTRs whose expression levels were depressed in Ab-challenged leaves in broccoli. Among them, the BolSULTR2;1 gene emerged as a key player in the plant's response to Ab. Virus-induced gene silencing (VIGS) of BolSULTR2;1s resulted in elevated glutathione (GSH) levels and enhanced tolerance to Ab. Taken together, these findings underscore the role of BolSULTR2;1 in maintaining redox homeostasis and enhancing plant disease resistance, suggesting its potential as a target for genome editing to develop broccoli varieties with improved pathogen tolerance.
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Affiliation(s)
- Guize Wu
- Key Laboratory of Vegetable Biology of Yunnan Province, Yunnan Agricultural University, Kunming 650201, China
- Beijing Vegetable Research Center, National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- State Key Laboratory of Vegetable Biobreeding, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- Key Laboratory of Urban Agriculture (North China), Ministry of Agriculture and Rural Affairs, Beijing 100097, China
| | - Yunhua Ding
- Beijing Vegetable Research Center, National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- State Key Laboratory of Vegetable Biobreeding, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
| | - Ning Li
- Beijing Vegetable Research Center, National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- State Key Laboratory of Vegetable Biobreeding, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- Key Laboratory of Urban Agriculture (North China), Ministry of Agriculture and Rural Affairs, Beijing 100097, China
| | - Hongji Zhang
- Key Laboratory of Vegetable Biology of Yunnan Province, Yunnan Agricultural University, Kunming 650201, China
| | - Ning Liu
- Beijing Vegetable Research Center, National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- State Key Laboratory of Vegetable Biobreeding, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- Key Laboratory of Urban Agriculture (North China), Ministry of Agriculture and Rural Affairs, Beijing 100097, China
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Choi J, Jang Y, Paik HG, Ha MHJ, Kwon J. Gastroprotective Effects of Aqueous Extracts of Broccoli Stems on Acute Injury in Rats: A Comprehensive Evaluation of Gastric Function and Inflammatory Responses. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:89. [PMID: 39859072 PMCID: PMC11766675 DOI: 10.3390/medicina61010089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 12/26/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025]
Abstract
Background and Objectives: Acute gastric injury is a prevalent gastrointestinal disorder characterized by inflammation and damage to the stomach lining. In this study, we investigated the therapeutic potential effects of broccoli stem extract (BSE) against acute gastritis in a rat model. Materials and Methods: The antioxidant properties of BSE were evaluated through DPPH and ABTS radical scavenging activity assays and total polyphenol content analysis. Acute gastric injury was induced using 150 mM HCl/60% EtOH, and male SD rats (6-weeks old, n = 6/group) were administered BSE by oral gavage at concentrations of 50, 125, and 250 mg/kg. Results: The BSE 250 mg/kg group exhibited significant relief of clinical signs compared to the negative control group. In addition, the BSE 250 mg/kg group showed significant improvements in gastric tissue, including macroscopic reductions in ulcer size and improved overall gastric morphology as assessed through gross examination, as well as microscopic improvements such as reduced inflammation and the restoration of mucosal integrity observed in histopathological analysis. BSE modulated NF-κB signaling, decreased inflammatory cytokines (TNF-α, IL-1β, and IL-6), and increased PGE2 levels. Pyloric ligation experiments demonstrated reduced pepsin and gastric acid secretion. Improvements in gastric emptying and gastrointestinal motility were also observed in the BSE-treated group. Conclusions: These findings highlight the potential of BSE as an effective therapeutic agent for acute gastritis in rats, offering significant improvements in gastric damage, inflammation, and motility.
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Affiliation(s)
- Jihye Choi
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, 79 Gobong-ro, Iksan-si 54596, Jeollabuk-do, Republic of Korea; (J.C.); (Y.J.); (H.-G.P.)
| | - Yuseong Jang
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, 79 Gobong-ro, Iksan-si 54596, Jeollabuk-do, Republic of Korea; (J.C.); (Y.J.); (H.-G.P.)
| | - Hyeon-Gi Paik
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, 79 Gobong-ro, Iksan-si 54596, Jeollabuk-do, Republic of Korea; (J.C.); (Y.J.); (H.-G.P.)
| | - Melissa Hyun-Joo Ha
- Broccos, Room 503, 3-3 Jongangdae-ro, 296 beon-gil, Dong-gu, Busan 48730, Republic of Korea;
| | - Jungkee Kwon
- Department of Laboratory Animal Medicine, College of Veterinary Medicine, Jeonbuk National University, 79 Gobong-ro, Iksan-si 54596, Jeollabuk-do, Republic of Korea; (J.C.); (Y.J.); (H.-G.P.)
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Gao R, Liu P, Bi J, Jiang Y, Zhao T, Yuan X, Zhang C, Wang Y. The Effects of Different Thiol-Containing Compounds on the Degradation of Sulforaphene. Molecules 2024; 29:4328. [PMID: 39339323 PMCID: PMC11434082 DOI: 10.3390/molecules29184328] [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: 07/25/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), produced by myrosinase hydrolysis of glucoraphenin (4-methylsulfinyl-3-butenyl glucosinolate) found in radish seeds, is strongly associated with cancer prevention. In this study, we investigated the stability of SFE (purity above 98%) under various thiol-containing compounds at 25 °C, such as sodium hydrosulfide (NaHS), glutathione (GSH), and cysteine (Cys). We observed that the degradation of SFE was closely related to the presence and dissociation capacity of thiol-containing compounds in the solution, particularly the thiol group. We found that the degradation rate of SFE was influenced by incubation with NaHS, GSH, and Cys, with distinct degradation products detected for each of these thiol-containing compounds. Compared to GSH, sulfide and Cys played important roles in promoting the degradation of SFE. Furthermore, we found substantial quantities of hydrogen sulfide in conjunction with SFE during the hydrolysis process of seeds, and a heat treatment of the seeds resulted in increased production of SFE. However, the introduction of sulfide-oxidizing bacteria to the hydrolytic system did not exhibit any inhibitory effect on the degradation of SFE. These results provided a guideline for industries to improve the stability of SFE during preparation.
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Affiliation(s)
- Rui Gao
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Pingxiang Liu
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Jingxiu Bi
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Yuying Jiang
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Tong Zhao
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Xuexia Yuan
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Chao Zhang
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
| | - Yutao Wang
- Shandong Provincial Key Laboratory of Test Technology on Food Quality and Safety, Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan 250100, China
- Cooperative of Vegetable and Grain Cultivation, Liaocheng Yifeng Bloc, Liaocheng 252000, China
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Guo C, Liu Y, Fu H, Zhang X, Li M. Effect of cruciferous vegetable intake on cancer: An umbrella review of meta-analysis. J Food Sci 2024; 89:5230-5244. [PMID: 39138635 DOI: 10.1111/1750-3841.17300] [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: 03/07/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/15/2024]
Abstract
Previous systematic evaluations and meta-analyses of the relationship between cruciferous vegetable (CV) intake and cancer risk have yielded inconsistent results. Herein, we summarize and evaluate the existing data and examine the relationship between CV intake and cancer risk. We searched four databases for cancer risk as a key outcome indicator. AMSTAR-2 was used to evaluate the methodological quality of the included systematic reviews, PRISMA 2020 was used to evaluate the report quality, and corrected coverage area analysis was used to evaluate the duplication rate of the original documents. Overall, 22 meta-analyses involving 175 independent cancer studies were included. Evidence on lung, gastric, prostate, breast, endometrial, and ovarian cancer, as well as renal cell carcinoma, suggests a potential association between cancer and CV intake, which influences the risk of various cancers. Future research should focus on improving methods and techniques, controlling influencing factors, elucidating underlying mechanisms, and improving evidence quality to demonstrate the association between CV intake and cancer. The potential role of dietary CVs in cancer control has implications for public health policies.
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Affiliation(s)
- Chunyan Guo
- College of Pharmacy, Qiqihar Medical University, Qiqihar, China
- Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, Hohhot, China
- Inner Mongolia Traditional Chinese & Mongolian Medical Research Institute, Hohhot, China
| | - Yibo Liu
- Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, Hohhot, China
- Inner Mongolia Traditional Chinese & Mongolian Medical Research Institute, Hohhot, China
- Inner Mongolia Medical University, Hohhot, China
| | - Haiqi Fu
- Inner Mongolia Medical University, Hohhot, China
| | - Xinyu Zhang
- Inner Mongolia Medical University, Hohhot, China
| | - Minhui Li
- College of Pharmacy, Qiqihar Medical University, Qiqihar, China
- Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, Hohhot, China
- Inner Mongolia Traditional Chinese & Mongolian Medical Research Institute, Hohhot, China
- Inner Mongolia Medical University, Hohhot, China
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Barnum C, Cho MJ, Markel K, Shih PM. Engineering Brassica Crops to Optimize Delivery of Bioactive Products Postcooking. ACS Synth Biol 2024; 13:736-744. [PMID: 38412618 PMCID: PMC10949231 DOI: 10.1021/acssynbio.3c00676] [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: 11/09/2023] [Revised: 02/22/2024] [Accepted: 02/22/2024] [Indexed: 02/29/2024]
Abstract
Glucosinolates are plant-specialized metabolites that can be hydrolyzed by glycosyl hydrolases, called myrosinases, creating a variety of hydrolysis products that benefit human health. While cruciferous vegetables are a rich source of glucosinolates, they are often cooked before consumption, limiting the conversion of glucosinolates to hydrolysis products due to the denaturation of myrosinases. Here we screen a panel of glycosyl hydrolases for high thermostability and engineer the Brassica crop, broccoli (Brassica oleracea L.), for the improved conversion of glucosinolates to chemopreventive hydrolysis products. Our transgenic broccoli lines enabled glucosinolate hydrolysis to occur at higher cooking temperatures, 20 °C higher than in wild-type broccoli. The process of cooking fundamentally transforms the bioavailability of many health-relevant bioactive compounds in our diet. Our findings demonstrate the promise of leveraging genetic engineering to tailor crops with novel traits that cannot be achieved through conventional breeding and improve the nutritional properties of the plants we consume.
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Affiliation(s)
- Collin
R. Barnum
- Department
of Plant and Microbial Biology, University
of California, Berkeley, Berkeley, California 94270, United States
- Department
of Plant Biology, University of California
Davis, Davis, California 95616, United States
- Biochemistry,
Molecular, Cellular and Developmental Biology Graduate Group, University of California Davis, Davis, California 95616, United States
| | - Myeong-Je Cho
- Innovative
Genomics Institute, University of California,
Berkeley, Berkeley, California 94720, United States
| | - Kasey Markel
- Department
of Plant and Microbial Biology, University
of California, Berkeley, Berkeley, California 94270, United States
- Environmental
Genomics and Systems Biology Division, Lawrence
Berkeley National Laboratory, Berkeley, California 94710, United States
| | - Patrick M. Shih
- Department
of Plant and Microbial Biology, University
of California, Berkeley, Berkeley, California 94270, United States
- Innovative
Genomics Institute, University of California,
Berkeley, Berkeley, California 94720, United States
- Environmental
Genomics and Systems Biology Division, Lawrence
Berkeley National Laboratory, Berkeley, California 94710, United States
- Feedstocks
Division, Joint BioEnergy Institute, Emeryville, California 94608, United States
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Li M, Long J, Yang M, Pang Y, Chen B, Li H. The Intake of Cruciferous Vegetables and the Risk of Ovarian Cancer: A Systematic Review and Dose-Response Meta-Analysis. Gynecol Obstet Invest 2024; 89:351-362. [PMID: 38479372 DOI: 10.1159/000537692] [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: 10/21/2023] [Accepted: 02/01/2024] [Indexed: 10/03/2024]
Abstract
INTRODUCTION The link between cruciferous vegetables (CVs) and ovarian cancer (OC) is still uncertain. This meta-analysis is intended to investigate the association between CV consumption and the risk of OC, as well as to conduct a dose-response analysis to determine the degree of correlation between them. METHODS We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases between database creation and October 2023. The present meta-analysis has been duly registered and assigned the registration number CRD42023470299. This study followed the PRISMA guidelines. The statistical analysis was performed using Stata 14.0 software. RESULTS There were a total of 7 cohort studies and 7 case-control studies with 7,269 cases and 742,952 subjects. The combined relative risk (RR) of the highest intake of CVs was 0.90 (95% confidence intervals [CIs]: 0.84-0.96; I2 = 54.7%; p = 0.007) compared to the lowest intake of CVs. The odds ratio (OR) was 0.97 (95% CIs: 0.86-1.08; p = 0.192) for cohort studies, and the RR was 0.79 (95% CIs: 0.67-0.91; p = 0.167) for case-control studies. The intake of CVs and the risk of OC were linearly correlated. Adding 15 g of CVs to the diet each day decreased the likelihood of developing OC by almost 4% (RR = 0.963, 95% CIs: 0.905-1.025; p = 0.235). CONCLUSIONS Consumption of CVs may be linked to a lower risk of OC.
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Affiliation(s)
- Meiqiong Li
- Department of Gynaecology and Obstetrics, The Second Clinical Medical School of Inner Mongolia University for The Nationalities (Inner Mongolia Forestry General Hospital), Yakeshi, China
| | - Jiaye Long
- Department of Interventional Radiology, The Second Clinical Medical School of Inner Mongolia University for The Nationalities (Inner Mongolia Forestry General Hospital), Yakeshi, China
| | - Miyang Yang
- Department of Radiology, The First Clinical Medical College, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yingrong Pang
- Department of Cardiology, The Second Clinical Medical School of Inner Mongolia University for The Nationalities (Inner Mongolia Forestry General Hospital), Yakeshi, China
| | - Baoxiang Chen
- Department of Interventional Radiology, The Second Clinical Medical School of Inner Mongolia University for The Nationalities (Inner Mongolia Forestry General Hospital), Yakeshi, China
- Department of Interventional Therapy, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China
| | - Hong Li
- Department of Gynaecology and Obstetrics, The Second Clinical Medical School of Inner Mongolia University for The Nationalities (Inner Mongolia Forestry General Hospital), Yakeshi, China
- Department of Gynaecology and Obstetrics, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China
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Zhang L, Kawaguchi R, Enomoto T, Nishida S, Burow M, Maruyama-Nakashita A. Glucosinolate Catabolism Maintains Glucosinolate Profiles and Transport in Sulfur-Starved Arabidopsis. PLANT & CELL PHYSIOLOGY 2023; 64:1534-1550. [PMID: 37464897 DOI: 10.1093/pcp/pcad075] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 07/06/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023]
Abstract
Glucosinolates (GSLs) are sulfur (S)-rich specialized metabolites present in Brassicales order plants. Our previous study found that GSL can function as a S source in Arabidopsis seedlings via its catabolism catalyzed by two β-glucosidases (BGLUs), BGLU28 and BGLU30. However, as GSL profiles in plants vary among growth stages and organs, the potential contribution of BGLU28/30-dependent GSL catabolism at the reproductive growth stage needs verification. Thus, in this study, we assessed growth, metabolic and transcriptional phenotypes of mature bglu28/30 double mutants grown under different S conditions. Our results showed that compared to wild-type plants grown under -S, mature bglu28/30 mutants displayed impaired growth and accumulated increased levels of GSL in their reproductive organs and rosette leaves of before-bolting plants. In contrast, the levels of primary S-containing metabolites, glutathione and cysteine decreased in their mature seeds. Furthermore, the transport of GSL from rosette leaves to the reproductive organs was stimulated in the bglu28/30 mutants under -S. Transcriptome analysis revealed that genes related to other biological processes, such as ethylene response, defense response and plant response to heat, responded differentially to -S in the bglu28/30 mutants. Altogether, these findings broadened our understanding of the roles of BGLU28/30-dependent GSL catabolism in plant adaptation to nutrient stress.
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Affiliation(s)
- Liu Zhang
- Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395 Japan
| | - Ryota Kawaguchi
- Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395 Japan
| | - Takuo Enomoto
- Department of Biological Science Course, Faculty of Agriculture, Saga University, Saga, 840-8502 Japan
- Institute of Fruit Tree and Tea Science, National Agriculture and Food Research Organization, Shimada, 428-8501 Japan
| | - Sho Nishida
- Department of Biological Science Course, Faculty of Agriculture, Saga University, Saga, 840-8502 Japan
| | - Meike Burow
- Department of Plant and Environmental Sciences, DynaMo Center, University of Copenhagen, Frederiksberg DK-1871, Denmark
- Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg DK-1871, Denmark
| | - Akiko Maruyama-Nakashita
- Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, 819-0395 Japan
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Hou Y, Li J, Ying S. Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer. Metabolites 2023; 13:1166. [PMID: 37999261 PMCID: PMC10673612 DOI: 10.3390/metabo13111166] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/16/2023] [Accepted: 11/18/2023] [Indexed: 11/25/2023] Open
Abstract
Tryptophan metabolism and gut microbiota form an integrated regulatory axis that impacts immunity, metabolism, and cancer. This review consolidated current knowledge on the bidirectional interactions between microbial tryptophan processing and the host. We focused on how the gut microbiome controls tryptophan breakdown via the indole, kynurenine, and serotonin pathways. Dysbiosis of the gut microbiota induces disruptions in tryptophan catabolism which contribute to disorders like inflammatory conditions, neuropsychiatric diseases, metabolic syndromes, and cancer. These disruptions affect immune homeostasis, neurotransmission, and gut-brain communication. Elucidating the mechanisms of microbial tryptophan modulation could enable novel therapeutic approaches like psychobiotics and microbiome-targeted dietary interventions. Overall, further research on the microbiota-tryptophan axis has the potential to revolutionize personalized diagnostics and treatments for improving human health.
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Affiliation(s)
- Yingjian Hou
- Target Discovery Center, China Pharmaceutical University, Nanjing 211198, China;
| | - Jing Li
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha 410000, China
| | - Shuhuan Ying
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
- Shanghai Bocimed Pharmaceutical Research Co., Ltd., Shanghai 201203, China
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Citi V, Barresi E, Piragine E, Spezzini J, Testai L, Da Settimo F, Martelli A, Taliani S, Calderone V. Anti-Proliferative Properties of the Novel Hybrid Drug Met-ITC, Composed of the Native Drug Metformin with the Addition of an Isothiocyanate H 2S Donor Moiety, in Different Cancer Cell Lines. Int J Mol Sci 2023; 24:16131. [PMID: 38003321 PMCID: PMC10671447 DOI: 10.3390/ijms242216131] [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: 09/27/2023] [Revised: 10/30/2023] [Accepted: 11/01/2023] [Indexed: 11/26/2023] Open
Abstract
Metformin (Met) is the first-line therapy in type 2 diabetes mellitus but, in last few years, it has also been evaluated as anti-cancer agent. Several pathways, such as AMPK or PI3K/Akt/mTOR, are likely to be involved in the anti-cancer Met activity. In addition, hydrogen sulfide (H2S) and H2S donors have been described as anti-cancer agents affecting cell-cycle and inducing apoptosis. Among H2S donors, isothiocyanates are endowed with a further anti-cancer mechanism: the inhibition of the histone deacetylase enzymes. On this basis, a hybrid molecule (Met-ITC) obtained through the addition of an isothiocyanate moiety to the Met molecule was designed and its ability to release Met has been demonstrated. Met-ITC exhibited more efficacy and potency than Met in inhibiting cancer cells (AsPC-1, MIA PaCa-2, MCF-7) viability and it was less effective on non-tumorigenic cells (MCF 10-A). The ability of Met-ITC to release H2S has been recorded both in cell-free and in cancer cells assays. Finally, its ability to affect the cell cycle and to induce both early and late apoptosis has been demonstrated on the most sensitive cell line (MCF-7). These results confirmed that Met-ITC is a new hybrid molecule endowed with potential anti-cancer properties derived both from Met and H2S.
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Affiliation(s)
- Valentina Citi
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
| | - Elisabetta Barresi
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
- Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126 Pisa, Italy
| | - Eugenia Piragine
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
| | - Jacopo Spezzini
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
| | - Lara Testai
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
- Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126 Pisa, Italy
- Interdepartmental Research Center “Biology and Pathology of Ageing”, University of Pisa, 56126 Pisa, Italy
| | - Federico Da Settimo
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
- Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126 Pisa, Italy
| | - Alma Martelli
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
- Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126 Pisa, Italy
- Interdepartmental Research Center “Biology and Pathology of Ageing”, University of Pisa, 56126 Pisa, Italy
| | - Sabrina Taliani
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
- Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126 Pisa, Italy
| | - Vincenzo Calderone
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; (V.C.); (E.B.); (E.P.); (J.S.); (L.T.); (F.D.S.); (S.T.); (V.C.)
- Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Lungarno Pacinotti 43/44, 56126 Pisa, Italy
- Interdepartmental Research Center “Biology and Pathology of Ageing”, University of Pisa, 56126 Pisa, Italy
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Babbar R, Vanya, Bassi A, Arora R, Aggarwal A, Wal P, Dwivedi SK, Alolayan S, Gulati M, Vargas-De-La-Cruz C, Behl T, Ojha S. Understanding the promising role of antibody drug conjugates in breast and ovarian cancer. Heliyon 2023; 9:e21425. [PMID: 38027672 PMCID: PMC10660083 DOI: 10.1016/j.heliyon.2023.e21425] [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: 07/25/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
A nascent category of anticancer therapeutic drugs called antibody-drug conjugates (ADCs) relate selectivity of aimed therapy using chemotherapeutic medicines with high cytotoxic power. Progressive linker technology led to the advancement of more efficacious and safer treatments. It offers neoteric as well as encouraging therapeutic strategies for treating cancer. ADCs selectively administer a medication by targeting antigens which are abundantly articulated on the membrane surface of tumor cells. Tumor-specific antigens are differently expressed in breast and ovarian cancers and can be utilized to direct ADCs. Compared to conventional chemotherapeutic drugs, this approach enables optimal tumor targeting while minimizing systemic damage. A cleavable linker improves the ADCs because it allows the toxic payload to be distributed to nearby cells that do not express the target protein, operating on assorted tumors with dissimilar cell aggregation. Presently fifteen ADCs are being studied in breast and ovarian carcinoma preclinically, and assortment of few have already undergone promising early-phase clinical trial testing. Furthermore, Phase I and II studies are investigating a wide variety of ADCs, and preliminary findings are encouraging. An expanding sum of ADCs will probably become feasible therapeutic choices as solo agents or in conjunction with chemotherapeutic agents. This review accentuates the most recent preclinical findings, pharmacodynamics, and upcoming applications of ADCs in breast and ovarian carcinoma.
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Affiliation(s)
- Ritchu Babbar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
| | - Vanya
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
| | - Aarti Bassi
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
| | - Rashmi Arora
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
| | - Ankur Aggarwal
- Institute of Pharmaceutical Sciences and Research, Gwalior, Madhya Pradesh, India
| | - Pranay Wal
- Pranveer Singh Institute of Technology, Pharmacy, NH-19 Bhauti, Kanpur, Uttar Pradesh, India
| | | | - Salma Alolayan
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraidah, 51452, Kingdom of Saudi Arabia
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 1444411, India
- ARCCIM, Faculty of Health, University of Technology Sydney, Ultimo, NSW, 20227, Australia
| | - Celia Vargas-De-La-Cruz
- Department of Pharmacology, Faculty of Pharmacy and Biochemistry, Bromatology and Toxicology, Universidad Nacional Mayor de San Marcos, Lima, 150001, Peru
- E-Health Research Center, Universidad de Ciencias y Humanidades, Lima, 15001, Peru
| | - Tapan Behl
- Amity School of Pharmaceutical Sciences, Amity University, Punjab, 140306, India
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, P.O. Box 15551, United Arab Emirates
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11
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Kanna GP, Kumar SJKJ, Kumar Y, Changela A, Woźniak M, Shafi J, Ijaz MF. Advanced deep learning techniques for early disease prediction in cauliflower plants. Sci Rep 2023; 13:18475. [PMID: 37891188 PMCID: PMC10611743 DOI: 10.1038/s41598-023-45403-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023] Open
Abstract
Agriculture plays a pivotal role in the economies of developing countries by providing livelihoods, sustenance, and employment opportunities in rural areas. However, crop diseases pose a significant threat to both farmers' incomes and food security. Furthermore, these diseases also show adverse effects on human health by causing various illnesses. Till date, only a limited number of studies have been conducted to identify and classify diseased cauliflower plants but they also face certain challenges such as insufficient disease surveillance mechanisms, the lack of comprehensive datasets that are properly labelled as well as are of high quality, and the considerable computational resources that are necessary for conducting thorough analysis. In view of the aforementioned challenges, the primary objective of this manuscript is to tackle these significant concerns and enhance understanding regarding the significance of cauliflower disease identification and detection in rural agriculture through the use of advanced deep transfer learning techniques. The work is conducted on the four classes of cauliflower diseases i.e. Bacterial spot rot, Black rot, Downy Mildew, and No disease which are taken from VegNet dataset. Ten deep transfer learning models such as EfficientNetB0, Xception, EfficientNetB1, MobileNetV2, EfficientNetB2, DenseNet201, EfficientNetB3, InceptionResNetV2, EfficientNetB4, and ResNet152V2, are trained and examined on the basis of root mean square error, recall, precision, F1-score, accuracy, and loss. Remarkably, EfficientNetB1 achieved the highest validation accuracy (99.90%), lowest loss (0.16), and root mean square error (0.40) during experimentation. It has been observed that our research highlights the critical role of advanced CNN models in automating cauliflower disease detection and classification and such models can lead to robust applications for cauliflower disease management in agriculture, ultimately benefiting both farmers and consumers.
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Affiliation(s)
- G Prabu Kanna
- School of Computer Science and Engineering, VIT Bhopal University, Bhopal-Indore Highway, Kothrikalan, Sehore Madhya Pradesh - 466114, India
| | - S J K Jagadeesh Kumar
- Department of Computer Science and Engineering, Kathir College of Engineering, Neelambur, India
| | - Yogesh Kumar
- Department of CSE, School of Technology, Pandit Deendayal Energy University, Gandhinagar, Gujarat, India.
| | - Ankur Changela
- Department of ICT, School of Technology, Pandit Deendayal Energy University, Gandhinagar, Gujarat, India
| | - Marcin Woźniak
- Faculty of Applied Mathematics, Silesian University of Technology, 44-100, Gliwice, Poland
| | - Jana Shafi
- Department of Computer Science, College of Arts and Science, Prince Sattam bin Abdul Aziz University, 11991, Wadi Ad-Dawasir, Saudi Arabia
| | - Muhammad Fazal Ijaz
- School of IT and Engineering, Melbourne Institute of Technology, Melbourne, 3000, Australia.
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12
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Khan F, Joshi A, Devkota HP, Subramaniyan V, Kumarasamy V, Arora J. Dietary glucosinolates derived isothiocyanates: chemical properties, metabolism and their potential in prevention of Alzheimer's disease. Front Pharmacol 2023; 14:1214881. [PMID: 37554984 PMCID: PMC10404612 DOI: 10.3389/fphar.2023.1214881] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 07/04/2023] [Indexed: 08/10/2023] Open
Abstract
Alzheimer's disease (AD) is the most prevalent form of dementia affecting millions of people worldwide. It is a progressive, irreversible, and incurable neurodegenerative disorder that disrupts the synaptic communication between millions of neurons, resulting in neuronal death and functional loss due to the abnormal accumulation of two naturally occurring proteins, amyloid β (Aβ) and tau. According to the 2018 World Alzheimer's Report, there is no single case of an Alzheimer's survivor; even 1 in 3 people die from Alzheimer's disease, and it is a growing epidemic across the globe fruits and vegetables rich in glucosinolates (GLCs), the precursors of isothiocyanates (ITCs), have long been known for their pharmacological properties and recently attracted increased interest for the possible prevention and treatment of neurodegenerative diseases. Epidemiological evidence from systematic research findings and clinical trials suggests that nutritional and functional dietary isothiocyanates interfere with the molecular cascades of Alzheimer's disease pathogenesis and prevent neurons from functional loss. The aim of this review is to explore the role of glucosinolates derived isothiocyanates in various molecular mechanisms involved in the progression of Alzheimer's disease and their potential in the prevention and treatment of Alzheimer's disease. It also covers the chemical diversity of isothiocyanates and their detailed mechanisms of action as reported by various in vitro and in vivo studies. Further clinical studies are necessary to evaluate their pharmacokinetic parameters and effectiveness in humans.
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Affiliation(s)
- Farhana Khan
- Laboratory of Bio-Molecular Technology, Department of Botany, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
| | - Abhishek Joshi
- Laboratory of Bio-Molecular Technology, Department of Botany, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
| | - Hari Prasad Devkota
- Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
| | - Vetriselvan Subramaniyan
- Department of Pharmacology, Center for Transdisciplinary Research, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
| | - Vinoth Kumarasamy
- Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Jaya Arora
- Laboratory of Bio-Molecular Technology, Department of Botany, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
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Abd Karim NA, Adam AHB, Jaafaru MS, Rukayadi Y, Abdull Razis AF. Apoptotic Potential of Glucomoringin Isothiocyanate (GMG-ITC) Isolated from Moringa oleifera Lam Seeds on Human Prostate Cancer Cells (PC-3). Molecules 2023; 28:molecules28073214. [PMID: 37049977 PMCID: PMC10096378 DOI: 10.3390/molecules28073214] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 01/27/2023] [Accepted: 02/08/2023] [Indexed: 04/14/2023] Open
Abstract
Inhibition of several protein pathways involved in cancer cell regulation is a necessary key in the discovery of cancer chemotherapy. Moringa oleifera Lam is often used in traditional medicine for the treatment of various illnesses. The plant contains glucomoringin isothiocyanate (GMG-ITC) with therapeutic potential against various cancer cells. Therefore, GMG-ITC was evaluated for its cytotoxicity against the PC-3 prostate cancer cell line and its potential to induce apoptosis. GMG-ITC inhibited cell proliferation in the PC-3 cell line with IC50 value 3.5 µg/mL. Morphological changes as a result of GMG-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GMG-ITC in a time-dependent manner. Moreover, GMG-ITC induced a time-dependent G2/M phase arrest, with reduction of 39.1% in the PC-3 cell line. GMG-ITC also activates apoptotic genes including caspase, tumor suppressor gene (p53), Akt/MAPK, and Bax of the proapoptotic Bcl family. Early apoptosis proteins (JNK, Bad, Bcl2, and p53) were significantly upregulated upon GMG-ITC treatment. It is concluded that apoptosis induction was observed in PC-3 cells treated with GMG-ITC. These phenomena suggest that GMG-ITC from M. oleifera seeds could be useful as a future cytotoxic agent against prostate cancer.
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Affiliation(s)
- Nurul Ashikin Abd Karim
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Aziza Hussein Bakheit Adam
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Department of Food Hygiene and Safety, Faculty of Public and Environmental Health, University of Khartoum, Khartoum 11111, Sudan
| | - Mohammed Sani Jaafaru
- Medical Analysis Department, Faculty of Science, Tishk International University, Erbil 44001, Iraq
| | - Yaya Rukayadi
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Ahmad Faizal Abdull Razis
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Laboratory of Food Safety and Food Integrity, Institute of Tropical Agriculture and Food Security, Universiti Putra Malaysia, Serdang 43400, Malaysia
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14
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Šola I, Davosir D, Kokić E, Zekirovski J. Effect of Hot- and Cold-Water Treatment on Broccoli Bioactive Compounds, Oxidative Stress Parameters and Biological Effects of Their Extracts. PLANTS (BASEL, SWITZERLAND) 2023; 12:1135. [PMID: 36903996 PMCID: PMC10005114 DOI: 10.3390/plants12051135] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/21/2023] [Accepted: 02/25/2023] [Indexed: 06/18/2023]
Abstract
The goal of this work was to define resistant and susceptible variables of young broccoli (Brassica oleracea L. convar. botrytis (L.) Alef. var. cymosa Duch.) plants treated with cold and hot water. Additionally, we wanted to single out variables that could potentially be used as biomarkers of cold/hot-water stress in broccoli. Hot water changed more variables (72%) of young broccoli than cold water (24%) treatment. Hot water increased the concentration of vitamin C for 33%, hydrogen peroxide for 10%, malondialdehyde for 28%, and proline for 147%. Extracts of broccoli stressed with hot water were significantly more efficient in the inhibition of α-glucosidase (65.85 ± 4.85% compared to 52.00 ± 5.16% of control plants), while those of cold-water-stressed broccoli were more efficient in the inhibition of α-amylase (19.85 ± 2.70% compared to 13.26 ± 2.36% of control plants). Total glucosinolates and soluble sugars were affected by hot and cold water in an opposite way, which is why they could be used as biomarkers of hot/cold-water stress in broccoli. The possibility of using temperature stress to grow broccoli enriched with compounds of interest to human health should be further investigated.
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Penta D, Natesh J, Mondal P, Meeran SM. Dietary Diindolylmethane Enhances the Therapeutic Effect of Centchroman in Breast Cancer by Inhibiting Neoangiogenesis. Nutr Cancer 2023; 75:734-749. [PMID: 36370104 DOI: 10.1080/01635581.2022.2143825] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Tumor angiogenesis is primarily regulated by vascular endothelial growth factor and its receptor (VEGF-VEGFR) communication, which is involved in cancer cell growth, progression, and metastasis. Diindolylmethane (DIM), a dietary bioactive from cruciferous vegetables, has been extensively studied in preclinical models for breast cancer prevention and treatment. Nevertheless, the possible role of DIM in the angiogenesis and metastasis regulations in triple-negative breast cancer (TNBC) remains elusive. Here, we investigated the potential anti-angiogenic and anti-metastatic role of DIM in combination with centchroman (CC). We observed that the oral administration of the DIM and CC combination suppressed primary tumor growth and tumor-associated vascularization in 4T1 tumors. Further, the DIM and CC combination exhibited a strong inhibitory effect on VEGF-induced angiogenesis in matrigel plugs. The mechanistic study demonstrated that DIM and CC could effectively downregulate VEGFA expression in tumor tissue and strongly interact with VEGFR2 to block its kinase activity. Interestingly, the DIM and CC combination also suppressed the lung metastasis of the highly metastatic 4T1 tumors through the downregulation of FAK/MMP9/2 signaling and reversal of epithelial-to-mesenchymal transition (EMT). Overall, these findings suggest that DIM-based nutraceuticals and functional foods can be developed as adjuvant therapy for treating TNBC.
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Affiliation(s)
- Dhanamjai Penta
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Jagadish Natesh
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Priya Mondal
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Syed Musthapa Meeran
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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16
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Casajús V, Howe K, Fish T, Civello P, Thannhauser T, Li L, Gómez Lobato M, Martínez G. Evidence of glucosinolates translocation from inflorescences to stems during postharvest storage of broccoli. PLANT PHYSIOLOGY AND BIOCHEMISTRY : PPB 2023; 195:322-329. [PMID: 36669347 DOI: 10.1016/j.plaphy.2023.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 12/05/2022] [Accepted: 01/09/2023] [Indexed: 06/17/2023]
Abstract
Broccoli is a vegetable appreciated by consumers for its nutritional properties, particularly for its high glucosinolate (GLS) content. However, broccoli shows a high rate of senescence during postharvest and the GLS content in inflorescences decreases sharply. Usually, postharvest studies on broccoli focus on inflorescences, ignoring the other tissues harvested such as the stems and main stalk. In this work, GLS metabolism in whole heads of broccoli (including inflorescences, small stems and stalk) was analysed during postharvest senescence. The content of GLS content, expression of GLS metabolic genes, and expression of GLS transport-associated genes were measured in the three parts of harvested broccoli. A marked decrease in the content of all GLSs was detected in inflorescences, but an increase in the stems and stalk. Also, decreased expressions of GLS biosynthesis and degradation genes were detected in all tissues analysed. On the other hand, an increase in the expression of one of the genes involved in GLS transport was observed. These results suggest that GLSs would be transported from inflorescences to stems during postharvest senescence. From a commercial point of view, broccoli stems are usually discarded and not used as food. However, the accumulation of GLSs in the stems is an important factor to consider when contemplating potential commercial use of this part of the plant.
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Affiliation(s)
- Victoria Casajús
- Instituto de Fisiología Vegetal (INFIVE) UNLP-CONICET, 113 and 61, 1900, La Plata, Argentina
| | - Kevin Howe
- Robert W. Holley Center for Agriculture and Health, USDA-Agricultural Research Service, Cornell University, Ithaca, NY, 14853, USA
| | - Tara Fish
- Robert W. Holley Center for Agriculture and Health, USDA-Agricultural Research Service, Cornell University, Ithaca, NY, 14853, USA
| | - Pedro Civello
- Instituto de Fisiología Vegetal (INFIVE) UNLP-CONICET, 113 and 61, 1900, La Plata, Argentina; Facultad de Ciencias Exactas. Universidad Nacional de La Plata (UNLP), La Plata, Argentina
| | - Theodore Thannhauser
- Robert W. Holley Center for Agriculture and Health, USDA-Agricultural Research Service, Cornell University, Ithaca, NY, 14853, USA
| | - Li Li
- Robert W. Holley Center for Agriculture and Health, USDA-Agricultural Research Service, Cornell University, Ithaca, NY, 14853, USA
| | - María Gómez Lobato
- Instituto de Fisiología Vegetal (INFIVE) UNLP-CONICET, 113 and 61, 1900, La Plata, Argentina
| | - Gustavo Martínez
- Instituto de Fisiología Vegetal (INFIVE) UNLP-CONICET, 113 and 61, 1900, La Plata, Argentina; Facultad de Ciencias Exactas. Universidad Nacional de La Plata (UNLP), La Plata, Argentina.
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17
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Hepatoprotective Effects of Radish ( Raphanus sativus L.) on Acetaminophen-Induced Liver Damage via Inhibiting Oxidative Stress and Apoptosis. Nutrients 2022; 14:nu14235082. [PMID: 36501112 PMCID: PMC9737327 DOI: 10.3390/nu14235082] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/31/2022] [Accepted: 11/09/2022] [Indexed: 12/03/2022] Open
Abstract
Alcohol and drug overdoses cause liver diseases such as cirrhosis, hepatitis, and liver cancer globally. In particular, an overdose of acetaminophen (APAP), which is generally used as an analgesic and antipyretic agent, is a major cause of acute hepatitis, and cases of APAP-induced liver damage are steadily increasing. Potential antioxidants may inhibit the generation of free radicals and prevent drug-induced liver damage. Among plant-derived natural materials, radishes (RJ) and turnips (RG) have anti-inflammatory, anticancer, and antioxidant properties due to the presence of functional ingredients, such as glucosinolate and isothiocyanate. Although various functions have been reported, in vivo studies on the antioxidant activity of radishes are insufficient. Therefore, we aim to evaluate the hepatoprotective effects of RG and RJ in APAP-induced liver-damaged mice. RG and RJ extracts markedly improved the histological status, such as inflammation and infiltration, of mice liver tissue, significantly decreased the levels of alanine transaminase, aspartate aminotransferase, and malondialdehyde, and significantly increased the levels of glutathione, superoxide dismutase and catalase in the APAP-induced liver-damaged mice. In addition, RG and RJ extracts significantly increased the expression of Nrf-2 and HO-1, which are antioxidative-related factors, and regulated the BAX and BCL-2, thereby showing anti-apoptosis activity. These results indicated that RG and RJ extracts protected mice against acute liver injury, attributed to a reduction in both oxidative stress and apoptosis. These findings have clinical implications for the use of RG and RJ extracts as potential natural candidates for developing hepatoprotective agents.
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Molecular Pathways Related to Sulforaphane as Adjuvant Treatment: A Nanomedicine Perspective in Breast Cancer. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58101377. [PMID: 36295538 PMCID: PMC9610969 DOI: 10.3390/medicina58101377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/23/2022] [Accepted: 09/28/2022] [Indexed: 11/06/2022]
Abstract
Because cancer is a multifactorial disease, it is difficult to identify the specific agents responsible for the disease's progression and development, but lifestyle and diet have been shown to play a significant role. Diverse natural compounds are demonstrating efficacy in the development of novel cancer therapies, including sulforaphane (1-isothiocyanate-4-(methylsulfinyl)butane), a compound found in broccoli and other cruciferous vegetables that promotes key biological processes such as apoptosis, cell cycle arrest, autophagy, and suppression of key signalling pathways such as the PI3K/AKT/mTOR pathway in breast cancer cells. However, one of the primary challenges with sulforaphane treatment is its low solubility in water and oral bioavailability. As a consequence, several investigations were conducted using this component complexed in nanoparticles, which resulted in superior outcomes when combined with chemotherapy drugs. In this study, we discuss the properties and benefits of sulforaphane in cancer therapy, as well as its ability to form complexes with nanomolecules and chemotherapeutic agents that synergize the antitumour response in breast cancer cells.
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Kapsetaki SE, Marquez Alcaraz G, Maley CC, Whisner CM, Aktipis A. Diet, Microbes, and Cancer Across the Tree of Life: a Systematic Review. Curr Nutr Rep 2022; 11:508-525. [PMID: 35704266 PMCID: PMC9197725 DOI: 10.1007/s13668-022-00420-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE OF REVIEW Cancers are a leading cause of death in humans and for many other species. Diet has often been associated with cancers, and the microbiome is an essential mediator between diet and cancers. Here, we review the work on cancer and the microbiome across species to search for broad patterns of susceptibility associated with different microbial species. RECENT FINDINGS Some microbes, such as Helicobacter bacteria, papillomaviruses, and the carnivore-associated Fusobacteria, consistently induce tumorigenesis in humans and other species. Other microbes, such as the milk-associated Lactobacillus, consistently inhibit tumorigenesis in humans and other species. We systematically reviewed over a thousand published articles and identified links between diet, microbes, and cancers in several species of mammals, birds, and flies. Future work should examine a larger variety of host species to discover new model organisms for human preclinical trials, to better understand the observed variance in cancer prevalence across species, and to discover which microbes and diets are associated with cancers across species. Ultimately, this could help identify microbial and dietary interventions to diagnose, prevent, and treat cancers in humans as well as other animals.
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Affiliation(s)
- Stefania E Kapsetaki
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA.
| | - Gissel Marquez Alcaraz
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Carlo C Maley
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Corrie M Whisner
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - Athena Aktipis
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Department of Psychology, Arizona State University, Tempe, AZ, USA
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20
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Microbiome in cancer: Role in carcinogenesis and impact in therapeutic strategies. Biomed Pharmacother 2022; 149:112898. [PMID: 35381448 DOI: 10.1016/j.biopha.2022.112898] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 11/21/2022] Open
Abstract
Cancer is the world's second-leading cause of death, and the involvement of microbes in a range of diseases, including cancer, is well established. The gut microbiota is known to play an important role in the host's health and physiology. The gut microbiota and its metabolites may activate immunological and cellular pathways that kill invading pathogens and initiate a cancer-fighting immune response. Cancer is a multiplex illness, characterized by the persistence of several genetic and physiological anomalies in malignant tissue, complicating disease therapy and control. Humans have coevolved with a complex bacterial, fungal, and viral microbiome over millions of years. Specific long-known epidemiological links between certain bacteria and cancer have recently been grasped at the molecular level. Similarly, advances in next-generation sequencing technology have enabled detailed research of microbiomes, such as the human gut microbiome, allowing for the finding of taxonomic and metabolomic linkages between the microbiome and cancer. These investigations have found causative pathways for both microorganisms within tumors and bacteria in various host habitats far from tumors using direct and immunological procedures. Anticancer diagnostic and therapeutic solutions could be developed using this review to tackle the threat of anti-cancer medication resistance as well through the wide-ranging involvement of the microbiota in regulating host metabolic and immunological homeostasis. We reviewed the significance of gut microbiota in cancer initiation as well as cancer prevention. We look at certain microorganisms that may play a role in the development of cancer. Several bacteria with probiotic qualities may be employed as bio-therapeutic agents to re-establish the microbial population and trigger a strong immune response to remove malignancies, and further study into this should be conducted.
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21
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Montano L, Maugeri A, Volpe MG, Micali S, Mirone V, Mantovani A, Navarra M, Piscopo M. Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids. Int J Mol Sci 2022; 23:ijms23031568. [PMID: 35163492 PMCID: PMC8836239 DOI: 10.3390/ijms23031568] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 01/24/2022] [Accepted: 01/27/2022] [Indexed: 02/04/2023] Open
Abstract
The role of environmental factors in influencing health status is well documented. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, dioxins, pesticides, ultrafine particles, produced by human activities put a strain on the body’s entire defense system. Therefore, together with public health measures, evidence-based individual resilience measures are necessary to mitigate cancer risk under environmental stress and to prevent reproductive dysfunction and non-communicable diseases; this is especially relevant for workers occupationally exposed to pollutants and/or populations residing in highly polluted areas. The Mediterranean diet is characterized by a high intake of fruits and vegetables rich in flavonoids, that can promote the elimination of pollutants in tissues and fluids and/or mitigate their effects through different mechanisms. In this review, we collected evidence from pre-clinical and clinical studies showing that the impairment of male fertility and gonadal development, as well as cancers of reproductive system, due to the exposure of organic and inorganic pollutants, may be counteracted by flavonoids.
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Affiliation(s)
- Luigi Montano
- Andrology Unit and Service of Lifestyle Medicine in UroAndrology, Local Health Authority (ASL), 84124 Salerno, Italy;
- PhD Program in Evolutionary Biology and Ecology, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Alessandro Maugeri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy;
| | - Maria Grazia Volpe
- Institute of Food Sciences, National Research Council, CNR, 83100 Avellino, Italy;
| | - Salvatore Micali
- Urology Department, University of Modena and Reggio Emilia, 41124 Modena, Italy;
| | - Vincenzo Mirone
- Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, 80126 Naples, Italy;
| | - Alberto Mantovani
- Department of Food, Safety, Nutrition and Veterinary public health, Italian National Health Institute, 00161 Roma, Italy;
| | - Michele Navarra
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy;
- Correspondence:
| | - Marina Piscopo
- Department of Biology, University of Naples Federico II, 80126 Napoli, Italy;
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Ngo SNT, Williams DB. Protective Effect of Isothiocyanates from Cruciferous Vegetables on Breast Cancer: Epidemiological and Preclinical Perspectives. Anticancer Agents Med Chem 2021; 21:1413-1430. [PMID: 32972351 DOI: 10.2174/1871520620666200924104550] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 07/26/2020] [Accepted: 08/09/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main Isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their anti-breast cancer effects. OBJECTIVE The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer. METHODS A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peer-reviewed studies of all types (in vitro studies, animal studies, and human studies) were selected. RESULTS The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed that sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways that promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemo-resistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively lower inhibitory concentration IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article. CONCLUSION Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane displaying the greatest potential.
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Affiliation(s)
- Suong N T Ngo
- School of Animal and Veterinary Sciences, The University of Adelaide, Adelaide, SA 5071, Australia
| | - Desmond B Williams
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia
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Casajús V, Civello P, Martínez G, Howe K, Fish T, Yang Y, Thannhauser T, Li L, Gómez Lobato M. Effect of continuous white light illumination on glucosinolate metabolism during postharvest storage of broccoli. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2021.111302] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Reyes Jara AM, Gómez-Lobato ME, Civello PM, Martínez GA. Expression of BoNOL and BoHCAR genes during postharvest senescence of broccoli heads. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2021; 101:1629-1635. [PMID: 32893880 DOI: 10.1002/jsfa.10783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/19/2020] [Accepted: 09/07/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Chlorophyll is the most abundant pigment on Earth, essential for the capture of light energy during photosynthesis. During senescence, chlorophyll degradation is highly regulated in order to diminish toxicity of the free chlorophyll molecule due to its photoactivity. The first step in the chlorophyll degradation pathway is the conversion of chlorophyll b to chlorophyll a by means of two consecutive reactions catalyzed by enzymes coded by NYC1 (NON-YELLOW COLORING 1), NOL (NYC1-LIKE) and HCAR. RESULTS In this work, we studied the expression of NOL and HCAR genes during postharvest senescence of broccoli. We found that the expression of BoNOL increase during the first days of storage and then decrease. In the case of BoHCAR, its expression is maintained during the first days and then it also diminishes. Additionally, the effect of different postharvest treatments on the expression of these genes was also analyzed. It was observed that the expression of BoNOL is lower in the treatments performed with 1-methylcyclopropene (1-MCP), 6-benzylaminopurine (6-BAP) and modified atmospheres, while BoHCAR expression showed an increase in these same treatments, and a decrease in the treatment with ethylene. There were no variations in the expression of both genes in heat treatment, UV-C treatment and visible light treatment. CONCLUSIONS These results suggest that both BoHCAR and BoNOL show a lower regulation of their expression than other genes involved in chlorophyll degradation during senescence. © 2020 Society of Chemical Industry.
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Affiliation(s)
| | | | - Pedro M Civello
- Instituto de Fisiología Vegetal (INFIVE) UNLP-Conicet, La Plata, Argentina
- Facultad de Ciencias Exactas UNLP, La Plata, Argentina
| | - Gustavo A Martínez
- Instituto de Fisiología Vegetal (INFIVE) UNLP-Conicet, La Plata, Argentina
- Facultad de Ciencias Exactas UNLP, La Plata, Argentina
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25
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Natural products in the reprogramming of cancer epigenetics. Toxicol Appl Pharmacol 2021; 417:115467. [PMID: 33631231 DOI: 10.1016/j.taap.2021.115467] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/15/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023]
Abstract
Owing to the technological advancements, including next generation sequencing, the significance of deregulated epigenetic mechanisms in cancer initiation, progression and treatment has become evident. The accumulating knowledge relating to the epigenetic markers viz. DNA methylation, Histone modifications and non-coding RNAs make them one of the most interesting candidates for developing anti-cancer therapies. The reversibility of deregulated epigenetic mechanisms through environmental and dietary factors opens numerous avenues in the field of chemoprevention and drug development. Recent studies have proven that plant-derived natural products encompass a great potential in targeting epigenetic signatures in cancer and numerous natural products are being explored for their possibility to be considered as "epi-drug". This review intends to highlight the major aberrant epigenetic mechanisms and summarizes the essential functions of natural products like Resveratrol, Quercetin, Genistein, EGCG, Curcumin, Sulforaphane, Apigenin, Parthenolide and Berberine in modulating these aberrations. This knowledge along with the challenges and limitations in this field has potential and wider implications in developing novel and successful therapeutic strategies. The increased focus in the area will possibly provide a better understanding for the development of dietary supplements and/or drugs either alone or in combination. The interaction of epigenetics with different hallmarks of cancer and how natural products can be utilized to target them will also be interesting in the future therapeutic approaches.
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Mitsiogianni M, Kyriakou S, Anestopoulos I, Trafalis DT, Deligiorgi MV, Franco R, Pappa A, Panayiotidis MI. An Evaluation of the Anti-Carcinogenic Response of Major Isothiocyanates in Non-Metastatic and Metastatic Melanoma Cells. Antioxidants (Basel) 2021; 10:antiox10020284. [PMID: 33668498 PMCID: PMC7918923 DOI: 10.3390/antiox10020284] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/07/2021] [Accepted: 02/10/2021] [Indexed: 12/28/2022] Open
Abstract
Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim was to compare different endpoints of cytotoxicity (e.g., reactive oxygen species, intracellular glutathione content, cell cycle growth arrest, apoptosis and necrosis) descriptive of an anti-cancer response between non-metastatic and metastatic melanoma as well as non-melanoma epidermoid carcinoma and non-tumorigenic cells. Our results showed that exposure to isothiocyanates induced an increase in intracellular reactive oxygen species and glutathione contents between non-metastatic and metastatic melanoma cells. The distribution of cell cycle phases followed a similar pattern in a manner where non-metastatic and metastatic melanoma cells appeared to be growth arrested at the G2/M phase while elevated levels of metastatic melanoma cells were shown to be at sub G1 phase, an indicator of necrotic cell death. Finally, metastatic melanoma cells were more sensitive apoptosis and/or necrosis as higher levels were observed compared to non-melanoma epidermoid carcinoma and non-tumorigenic cells. In general, non-melanoma epidermoid carcinoma and non-tumorigenic cells were more resistant under any experimental exposure condition. Overall, our study provides further evidence for the potential development of isothiocyanates as promising anti-cancer agents against non-metastatic and metastatic melanoma cells, a property specific for these cells and not shared by non-melanoma epidermoid carcinoma or non-tumorigenic melanocyte cells.
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Affiliation(s)
- Melina Mitsiogianni
- Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK;
| | - Sotiris Kyriakou
- Department of Electron Microscopy & Molecular Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus; (S.K.); (I.A.)
- The Cyprus School of Molecular Medicine, P.O. Box 23462, Nicosia 1683, Cyprus
| | - Ioannis Anestopoulos
- Department of Electron Microscopy & Molecular Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus; (S.K.); (I.A.)
- The Cyprus School of Molecular Medicine, P.O. Box 23462, Nicosia 1683, Cyprus
| | - Dimitrios T. Trafalis
- Laboratory of Pharmacology, Medical School, National & Kapodistrian University of Athens, 11527 Athens, Greece; (D.T.T.); (M.V.D.)
| | - Maria V. Deligiorgi
- Laboratory of Pharmacology, Medical School, National & Kapodistrian University of Athens, 11527 Athens, Greece; (D.T.T.); (M.V.D.)
| | - Rodrigo Franco
- Redox Biology Centre, University of Nebraska-Lincoln, Lincoln, NE 68583, USA;
- Department of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
| | - Aglaia Pappa
- Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | - Mihalis I. Panayiotidis
- Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK;
- Department of Electron Microscopy & Molecular Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus; (S.K.); (I.A.)
- The Cyprus School of Molecular Medicine, P.O. Box 23462, Nicosia 1683, Cyprus
- Correspondence: ; Tel.: +357-223-92626
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27
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Intake of total cruciferous vegetable and its contents of glucosinolates and isothiocyanates, glutathione S-transferases polymorphisms and breast cancer risk: a case-control study in China. Br J Nutr 2020; 124:548-557. [PMID: 32308174 DOI: 10.1017/s0007114520001348] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Cruciferous vegetables contain high levels of glucosinolates (GSL) and isothiocyanates (ITC). ITC are known to induce glutathione S-transferases (GST) and thus exert their anticarcinogenic effects. This study explored the combined effects of cruciferous vegetable, GSL and ITC intake and GST polymorphisms on breast cancer risk. A total of 737 breast cancer cases and 756 controls were recruited into this case-control study. OR and 95 % CI were assessed by multivariable logistic regression. Higher cruciferous vegetable, GSL and ITC intakes were inversely associated with breast cancer risk, with adjusted OR of 0·48 (95 % CI 0·35, 0·65), 0·54 (95 % CI 0·40, 0·74) and 0·62 (95 % CI 0·45, 0·84), respectively. Compared with women carrying the GSTP1 rs1695 wild AA genotype and high cruciferous vegetable, GSL or ITC intake, carriers of the AA genotype with low cruciferous vegetable, GSL and ITC intake had greater risk of breast cancer, with adjusted OR of 1·43 (95 % CI 1·01, 1·87), 1·34 (95 % CI 1·02, 1·75) and 1·37 (95 % CI 1·05, 1·80), respectively. Persons with the GSTM1-null genotype and lower intake of cruciferous vegetables, GSL and ITC had higher risk of breast cancer than those with the GSTM1-present genotype and higher intake, with OR of 1·42 (95 % CI 1·04, 1·95), 1·43 (95 % CI 1·05, 1·96) and 1·45 (95 % CI 1·06, 1·98), respectively. Among women possessing the GSTT1-present genotype, low intake of cruciferous vegetables, GSL or ITC was associated with higher risk of breast cancer. But these interactions were non-significant. This study indicated that there were no significant interactions between cruciferous vegetable, GSL or ITC intake and GST polymorphisms on breast cancer risk.
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Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. Hispidulin: A promising flavonoid with diverse anti-cancer properties. Life Sci 2020; 259:118395. [PMID: 32905830 DOI: 10.1016/j.lfs.2020.118395] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 08/31/2020] [Accepted: 09/02/2020] [Indexed: 02/06/2023]
Abstract
In recent years, natural products have increasingly attracted more attention because of their potential anticancer activity and low intrinsic toxicity. Hispidulin is a natural flavonoid with a wide range of biological activities, including anti-inflammatory, antifungal, antiplatelet, anticonvulsant, anti-osteoporotic, and notably anticancer activities. Numerous in vivo and in vitro studies have shown that hispidulin, as a potential anticancer drug, affects cell proliferation, apoptosis, cell cycle, angiogenesis, and metastasis. Moreover, hispidulin exhibits synergistic anti-tumor effects when combined with some common clinical anticancer drugs (e.g., gemcitabine, 5-fluoroucil, sunitinib, temozolomide, and TRAIL). The combination of hispidulin and chemotherapeutic drugs reduces the efflux of chemotherapeutic drugs, enhances the chemosensitivity of cancer cells, and reverses drug resistance. Herein, we outlined the anticancer effects of hispidulin in various cancers and its intracellular molecular targets and related mechanisms of its anticancer activity. Based on the available literature, it can be established that hispidulin has significant potential to become an important complementary medicine for cancer prevention and treatment. However, more in-depth in vitro and in vivo studies should be conducted to support its translation from bench to bedside.
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Affiliation(s)
- Kaili Liu
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Fei Zhao
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Jingjing Yan
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Zhengchao Xia
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Dandan Jiang
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China
| | - Peizhi Ma
- Department of Pharmacy, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China; Department of Pharmacy, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China; Department of Pharmacy, People's Hospital of Henan University, School of Clinical Medicine, Henan University, Zhengzhou, China.
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Ahmed AG, Hussein UK, Ahmed AE, Kim KM, Mahmoud HM, Hammouda O, Jang KY, Bishayee A. Mustard Seed ( Brassica nigra) Extract Exhibits Antiproliferative Effect against Human Lung Cancer Cells through Differential Regulation of Apoptosis, Cell Cycle, Migration, and Invasion. Molecules 2020; 25:molecules25092069. [PMID: 32365503 PMCID: PMC7248788 DOI: 10.3390/molecules25092069] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/24/2020] [Accepted: 04/26/2020] [Indexed: 02/06/2023] Open
Abstract
Lung cancer is the primary cause of cancer-related death worldwide, and development of novel lung cancer preventive and therapeutic agents are urgently needed. Brassica nigra (black mustard) seeds are commonly consumed in several Asian and African countries. Mustard seeds previously exhibited significant anticancer activities against several cancer types. In the present study, we have investigated various cellular and molecular mechanisms of anticancer effects of an ethanolic extract of B. nigra seeds against A549 and H1299 human non-small cell lung cancer cell lines. B. nigra extract showed a substantial growth-inhibitory effect as it reduced the viability and clonogenic survival of A549 and H1299 cells in a concentration-dependent manner. B. nigra extract induced cellular apoptosis in a time- and concentration-dependent fashion as evidenced from increased caspase-3 activity. Furthermore, treatment of both A549 and H1299 cells with B. nigra extract alone or in combination with camptothecin induced DNA double-strand breaks as evidenced by upregulation of γH2A histone family member X, Fanconi anemia group D2 protein, Fanconi anemia group J protein, ataxia-telangiectesia mutated and Rad3-related protein. Based on cell cycle analysis, B. nigra extract significantly arrested A549 and H1299 cells at S and G2/M phases. Additionally, B. nigra extract suppressed the migratory and invasive properties of both cell lines, downregulated the expression of matrix metalloproteinase-2 (MMP2), MMP9, and Snail and upregulated the expression of E-cadherin at mRNA and protein levels. Taken together, these findings indicate that B. nigra seed extract may have an important anticancer potential against human lung cancer which could be mediated through simultaneous and differential regulation of proliferation, apoptosis, DNA damage, cell cycle, migration, and invasion.
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Affiliation(s)
- Asmaa Gamal Ahmed
- Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, Korea; (A.G.A.); (U.K.H.); (K.M.K.)
- Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62511, Egypt;
| | - Usama Khamis Hussein
- Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, Korea; (A.G.A.); (U.K.H.); (K.M.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54907, Korea
- Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt; (H.M.M.); (O.H.)
| | - Amr E. Ahmed
- Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62511, Egypt;
| | - Kyoung Min Kim
- Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, Korea; (A.G.A.); (U.K.H.); (K.M.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54907, Korea
| | - Hamada M. Mahmoud
- Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt; (H.M.M.); (O.H.)
| | - Ola Hammouda
- Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt; (H.M.M.); (O.H.)
| | - Kyu Yun Jang
- Department of Pathology, Chonbuk National University Medical School, Jeonju 54907, Korea; (A.G.A.); (U.K.H.); (K.M.K.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54907, Korea
- Correspondence: (K.Y.J.); or (A.B.); Tel.: +82-10-4228-9970 (K.Y.J.); +1-941-782-5950 (A.B.)
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
- Correspondence: (K.Y.J.); or (A.B.); Tel.: +82-10-4228-9970 (K.Y.J.); +1-941-782-5950 (A.B.)
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Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells. Molecules 2020; 25:molecules25051240. [PMID: 32182965 PMCID: PMC7179403 DOI: 10.3390/molecules25051240] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 12/02/2019] [Accepted: 12/05/2019] [Indexed: 01/26/2023] Open
Abstract
Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.
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Vanlalneihi B, Saha P, Kalia P, Jaiswal S, Kundu A, Saha ND, Sirowa SS, Singh N. Chemometric approach based characterization and selection of mid-early cauliflower for bioactive compounds and antioxidant activity. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2020; 57:293-300. [PMID: 31975732 PMCID: PMC6952495 DOI: 10.1007/s13197-019-04060-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 06/28/2019] [Accepted: 08/22/2019] [Indexed: 10/26/2022]
Abstract
The present study was aimed to analyse bioactive compounds (total phenolics, ascorbic acid and sinigrin) and antioxidant activity in 14 mid-early cauliflower genotypes. Significant differences (pb 0.05) were observed among the genotypes for all bioactive compounds and antioxidant activity. Total phenolics content of curd were ranged from 20.36 to 48.93 mg gallic acid equivalent (GAE) 100 g-1 fresh weight (FW) which showed 2.5 times variation. The ascorbic acid content was maximum in DC522 (88.53 mg 100 g-1 FW) followed by Pusa Sharad (65.64 mg 100 g-1 FW) while minimum in DC310 (39.62 65.64 mg 100 g-1 FW). Wide variation was observed for cupric reducing antioxidant capacity and ferric reducing antioxidant power ranging from 9.04 to 20.83 mg GAE 100 g-1 FW and 13.11 to 26.31 mg GAE 100 g-1 FW, respectively. Sinigrin was found to be highest in DC306 (39.50 µmol 100 g-1 FW) for leaf and in DC326 (36.93 µmol 100 g-1 FW) for curd sample. The cauliflower genotypes were classified based on chemometric approaches namely principal component analysis (PCA) and agglomerative hierarchical clustering (AHC). The first two principal components (PC1 and PC2) explained 50.62% and 23.28% of total variance, respectively. The AHC as revealed by heat map classified cauliflower genotypes into four main groups based on measured traits. The information is useful for developing varieties and/or hybrids rich in bioactive compounds and antioxidant activity.
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Affiliation(s)
- B. Vanlalneihi
- Division of Vegetable Science, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
- ICAR-Indian Institute of Horticultural Research, Bengaluru, 560 089 India
| | - Partha Saha
- Division of Vegetable Science, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - P. Kalia
- Division of Vegetable Science, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Sarika Jaiswal
- ICAR-Indian Agricultural Statistics Research Institute, New Delhi, 110012 India
| | - Aditi Kundu
- Division of Agricultural Chemicals, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - N. D. Saha
- CESCRA, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Shrawan Singh Sirowa
- Division of Vegetable Science, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Naveen Singh
- Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
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Donovan MG, Selmin OI, Stillwater BJ, Neumayer LA, Romagnolo DF. Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models. Front Nutr 2020; 7:571455. [PMID: 33123546 PMCID: PMC7573103 DOI: 10.3389/fnut.2020.571455] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 09/03/2020] [Indexed: 12/20/2022] Open
Abstract
Breast cancer is the most common malignancy and cause of cancer-related mortality among women worldwide. Triple negative breast cancers (TNBC) are the most aggressive and lethal of the breast cancer molecular subtypes, due in part to a poor understanding of TNBC etiology and lack of targeted therapeutics. Despite advances in the clinical management of TNBC, optimal treatment regimens remain elusive. Thus, identifying interventional approaches that suppress the initiation and progression of TNBC, while minimizing side effects, would be of great interest. Studies have documented an inverse relationship between the incidence of hormone receptor negative breast cancer and adherence to a Mediterranean Diet, particularly higher consumption of fish and olive oil. Here, we performed a review of studies over the last 5 years investigating the effects of fish oil, olive oil and their components in model systems of TNBC. We included studies that focused on the fish oil ω-3 essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in addition to olive oil polyphenolic compounds and oleic acid. Both beneficial and deleterious effects on TNBC model systems are reviewed and we highlight how multiple components of these Mediterranean Diet oils target signaling pathways known to be aberrant in TNBC including PI3K/Akt/mTOR, NF-κB/COX2 and Wnt/β-catenin.
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Affiliation(s)
- Micah G. Donovan
- Interdisciplinary Cancer Biology Graduate Program, The University of Arizona, Tucson, AZ, United States
| | - Ornella I. Selmin
- University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, United States
- Department of Nutritional Sciences, The University of Arizona, Tucson, AZ, United States
| | - Barbara J. Stillwater
- Department of Surgery, Breast Surgery Oncology, The University of Arizona, Tucson, AZ, United States
| | - Leigh A. Neumayer
- Department of Surgery, Breast Surgery Oncology, The University of Arizona, Tucson, AZ, United States
| | - Donato F. Romagnolo
- University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, United States
- Department of Nutritional Sciences, The University of Arizona, Tucson, AZ, United States
- *Correspondence: Donato F. Romagnolo
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Alhassan SO, Atawodi SEO. Chemopreventive effect of dietary inclusion with Crassocephalum rubens (Juss ex Jacq) leaf on N-methyl-N-nitrosourea (MNU)-induced colorectal carcinogenesis in Wistar rats. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.103589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Houghton CA. Sulforaphane: Its "Coming of Age" as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:2716870. [PMID: 31737167 PMCID: PMC6815645 DOI: 10.1155/2019/2716870] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 06/24/2019] [Accepted: 09/06/2019] [Indexed: 12/17/2022]
Abstract
A growing awareness of the mechanisms by which phytochemicals can influence upstream endogenous cellular defence processes has led to intensified research into their potential relevance in the prevention and treatment of disease. Pharmaceutical medicine has historically looked to plants as sources of the starting materials for drug development; however, the focus of nutraceutical medicine is to retain the plant bioactive in as close to its native state as possible. As a consequence, the potency of a nutraceutical concentrate or an extract may be lower than required for significant gene expression. The molecular structure of bioactive phytochemicals to a large extent determines the molecule's bioavailability. Polyphenols are abundant in dietary phytochemicals, and extensive in vitro research has established many of the signalling mechanisms involved in favourably modulating human biochemical pathways. Such pathways are associated with core processes such as redox modulation and immune modulation for infection control and for downregulating the synthesis of inflammatory cytokines. Although the relationship between oxidative stress and chronic disease continues to be affirmed, direct-acting antioxidants such as vitamins A, C, and E, beta-carotene, and others have not yielded the expected preventive or therapeutic responses, even though several large meta-analyses have sought to evaluate the potential benefit of such supplements. Because polyphenols exhibit poor bioavailability, few of their impressive in vitro findings have been replicated in vivo. SFN, an aliphatic isothiocyanate, emerges as a phytochemical with comparatively high bioavailability. A number of clinical trials have demonstrated its ability to produce favourable outcomes in conditions for which there are few satisfactory pharmaceutical solutions, foreshadowing the potential for SFN as a clinically relevant nutraceutical. Although myrosinase-inert broccoli sprout extracts are widely available, there now exist myrosinase-active broccoli sprout supplements that yield sufficient SFN to match the doses used in clinical trials.
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Glucosinolate-Degradation Products as Co-Adjuvant Therapy on Prostate Cancer in Vitro. Int J Mol Sci 2019; 20:ijms20204977. [PMID: 31600887 PMCID: PMC6834131 DOI: 10.3390/ijms20204977] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 10/01/2019] [Accepted: 10/08/2019] [Indexed: 12/12/2022] Open
Abstract
Glucosinolate-degradation products (GS-degradation products) are believed to be responsible for the anticancer effects of cruciferous vegetables. Furthermore, they could improve the efficacy and reduce side-effects of chemotherapy. The aim of the present study was to determine the cytotoxic effects of GS-degradation products on androgen-insensitive human prostate cancer (AIPC) PC-3 and DU 145 cells and investigate their ability to sensitize such cells to chemotherapeutic drug Docetaxel (DOCE). Cells were cultured under growing concentrations of allyl-isothiocyanate (AITC), sulforaphane (SFN), 4-pentenyl-isothiocyanate (4PI), iberin (IB), indole-3-carbinol (I3C), or phenethyl-isothiocyanate (PEITC) in absence or presence of DOCE. The anti-tumor effects of these compounds were analyzed using the trypan blue exclusion, apoptosis, invasion and RT-qPCR assays and confocal microscopy. We observed that AITC, SFN, IB, and/or PEITC induced a dose- and time-dependent cytotoxic effect on PC-3 and DU 145 cells, which was mediated, at least, by apoptosis and cell cycle arrest. Likewise, we showed that these GS-degradation products sensitized both cell lines to DOCE by synergic mechanisms. Taken together, our results indicate that GS-degradation products can be promising compounds as co-adjuvant therapy in prostate cancer.
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Hwang ES, Bornhorst GM, Oteiza PI, Mitchell AE. Assessing the Fate and Bioavailability of Glucosinolates in Kale ( Brassica oleracea) Using Simulated Human Digestion and Caco-2 Cell Uptake Models. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:9492-9500. [PMID: 31374175 DOI: 10.1021/acs.jafc.9b03329] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Glucosinolates and their hydrolysis products were characterized in fresh and in in vitro gastric and intestinal digesta of Dinosaur kale (Brassica oleracea L var. palmifolia DC). In fresh kale, glucoraphanin, sinigrin, gluconapin, gluconasturtiin, glucoerucin, glucobrasscin, and 4-methoxylglucobrassicin were identified. After 120 min of gastric digestion, the levels of glucoraphanin, sinigrin, and gluconapin decreased, and no glucoerucin or glucobrasscin was detected. However, a concomitant increase in the glucosinolate hydrolysis products allyl nitrile, 3-butenyl isothiocyanate, phenylacetonitrile, and sulforaphane was observed. This trend continued through intestinal digestion. After 120 min, the levels of allyl nitrile, 3-butenyl isothiocyanate, phenylacetonitrile, and sulforaphane were 88.19 ± 5.85, 222.15 ± 30.26, 129.17 ± 17.57, and 13.71 ± 0.62 pmol/g fresh weight, respectively. Intestinal digesta were then applied to Caco-2 cell monolayers to assess the bioavailability. After 6 h of incubation, no glucosinolates were detected and the percentage of total cellular uptake of the glucosinolate hydrolysis products ranged from 29.35% (sulforaphane) to 46.60% (allyl nitrile).
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Affiliation(s)
- Eun-Sun Hwang
- Department of Nutrition and Culinary Science , Hankyong National University , 327 Chungang-Ro , Anseong-Si , Kyonggi-do 17579 , Korea
| | - Gail M Bornhorst
- Department of Biological and Agricultural Engineering, Department of Food Science and Technology , University of California, Davis , One Shields Avenue , Davis , California 95616 , United States
- Department of Food Science and Technology , University of California, Davis , One Shields Avenue , Davis , California 95616 , United States
| | - Patricia I Oteiza
- Department of Nutrition and Department of Environmental Toxicology , University of California, Davis , One Shields Avenue , Davis , California 95616 , United States
| | - Alyson E Mitchell
- Department of Food Science and Technology , University of California, Davis , One Shields Avenue , Davis , California 95616 , United States
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Chen Y, Chen JQ, Ge MM, Zhang Q, Wang XQ, Zhu JY, Xie CF, Li XT, Zhong CY, Han HY. Sulforaphane inhibits epithelial-mesenchymal transition by activating extracellular signal-regulated kinase 5 in lung cancer cells. J Nutr Biochem 2019; 72:108219. [PMID: 31473507 DOI: 10.1016/j.jnutbio.2019.108219] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 06/06/2019] [Accepted: 07/24/2019] [Indexed: 12/27/2022]
Abstract
Epithelial-mesenchymal transition (EMT) contributes to the initiation, invasion, metastasis and drug resistance of cancer. The function of extracellular signal-regulated kinase 5 (ERK5) in lung cancer progression remains elusive. In this study, we investigated the effect of sulforaphane (SFN) on lung cancer EMT and the role of ERK5 in its effect. Wound healing and Transwell assays were applied to examine the migratory and invasive capacity in vitro. Quantitative real-time polymerase chain reaction and immunoblotting analysis were performed to investigate the expression of mRNA and protein levels. Small-interfering RNA was used to silence ERK5. Xenograft model was used to confirm the effect of SFN in vivo. Enhanced EMT and decreased ERK5 activation were observed in lung cancer cells in comparison with normal human bronchial epithelial cells. SFN diminished the migratory and invasive capacity of lung cancer cells. Additionally, significantly increased expression of epithelial markers (E-cadherin and ZO-1), decreased expression of mesenchymal markers (N-cadherin and Snail1) and activation of ERK5 were observed after SFN treatment. The inhibitory effect of SFN on lung cancer cell EMT was attenuated by ERK5 silencing. SFN-induced EMT suppression and ERK5 activation were further confirmed in lung cancer xenograft mouse model. The present study illustrated for the first time that ERK5 activation mediates SFN suppression of lung cancer cell EMT. These findings could provide new insights into the function of ERK5 in EMT regulation and the potential therapeutic application of SFN in cancer intervention.
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Affiliation(s)
- Yue Chen
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jia-Qi Chen
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Miao-Miao Ge
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Qi Zhang
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xue-Qi Wang
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jian-Yun Zhu
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China; Suzhou Digestive Diseases and Nutrition Research Center, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Chun-Feng Xie
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xiao-Ting Li
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Cai-Yun Zhong
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
| | - Hong-Yu Han
- Department of Clinical Nutrition, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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Hwang ES. Effect of Cooking Method on Antioxidant Compound Contents in Cauliflower. Prev Nutr Food Sci 2019; 24:210-216. [PMID: 31328127 PMCID: PMC6615361 DOI: 10.3746/pnf.2019.24.2.210] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 05/05/2019] [Indexed: 01/22/2023] Open
Abstract
In this study, we determined the contents of glucosinolate, polyphenol, and flavonoid, and the antioxidant activities of uncooked, steamed, and boiled cauliflower. Eight glucosinolate peaks were detected, representing glucoiberin, progoitrin, glucoraphanin, sinigrin, gluconapin, glucoiberverin, glucobrassicin, and gluconasturtiin. Boiled cauliflower contained significantly lowered concentrations of glucosinolate, total polyphenol, and total flavonoid compared to uncooked or steamed cauliflower. These results clearly indicate that health-promoting compounds in cauliflower are significantly impacted by different cooking methods: uncooked> steamed> boiled. The amounts of total polyphenols and total flavonoids in uncooked cauliflower extracted with 80% ethanol were higher than extracts of steamed and boiled cauliflower. The highest antioxidant activity was observed in uncooked cauliflower extracted using 80% ethanol compared to those extracted with water at the same concentration. Steamed and boiled cauliflower extracts also showed lower antioxidant activity than uncooked extracts. Based on these results, fresh uncooked cauliflower contains higher contents of health-promoting compounds and elevated antioxidant activity. Moreover, steaming may be more desirable than boiling in order to minimize loss of glucosinolates when storing, pretreating, processing, and cooking cruciferous vegetables.
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Affiliation(s)
- Eun-Sun Hwang
- Department of Nutrition and Culinary Science, Hankyong National University, Gyeonggi 17579, Korea
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Mitsiogianni M, Koutsidis G, Mavroudis N, Trafalis DT, Botaitis S, Franco R, Zoumpourlis V, Amery T, Galanis A, Pappa A, Panayiotidis MI. The Role of Isothiocyanates as Cancer Chemo-Preventive, Chemo-Therapeutic and Anti-Melanoma Agents. Antioxidants (Basel) 2019; 8:E106. [PMID: 31003534 PMCID: PMC6523696 DOI: 10.3390/antiox8040106] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 04/03/2019] [Accepted: 04/12/2019] [Indexed: 12/11/2022] Open
Abstract
Many studies have shown evidence in support of the beneficial effects of phytochemicals in preventing chronic diseases, including cancer. Among such phytochemicals, sulphur-containing compounds (e.g., isothiocyanates (ITCs)) have raised scientific interest by exerting unique chemo-preventive properties against cancer pathogenesis. ITCs are the major biologically active compounds capable of mediating the anticancer effect of cruciferous vegetables. Recently, many studies have shown that a higher intake of cruciferous vegetables is associated with reduced risk of developing various forms of cancers primarily due to a plurality of effects, including (i) metabolic activation and detoxification, (ii) inflammation, (iii) angiogenesis, (iv) metastasis and (v) regulation of the epigenetic machinery. In the context of human malignant melanoma, a number of studies suggest that ITCs can cause cell cycle growth arrest and also induce apoptosis in human malignant melanoma cells. On such basis, ITCs could serve as promising chemo-therapeutic agents that could be used in the clinical setting to potentiate the efficacy of existing therapies.
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Affiliation(s)
- Melina Mitsiogianni
- Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK.
| | - Georgios Koutsidis
- Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK.
| | - Nikos Mavroudis
- Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
| | - Dimitrios T Trafalis
- Laboratory of Pharmacology, Unit of Clinical Pharmacology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
| | - Sotiris Botaitis
- Second Department of Surgery, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
| | - Rodrigo Franco
- Redox Biology Centre, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
- School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
| | - Vasilis Zoumpourlis
- Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece.
| | - Tom Amery
- The Watrercress Company / The Wasabi Company, Waddock, Dorchester, Dorset DT2 8QY, UK.
| | - Alex Galanis
- Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
| | - Aglaia Pappa
- Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
| | - Mihalis I Panayiotidis
- Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK.
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Whisner CM, Athena Aktipis C. The Role of the Microbiome in Cancer Initiation and Progression: How Microbes and Cancer Cells Utilize Excess Energy and Promote One Another's Growth. Curr Nutr Rep 2019; 8:42-51. [PMID: 30758778 PMCID: PMC6426824 DOI: 10.1007/s13668-019-0257-2] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW We use an ecological lens to understand how microbes and cancer cells coevolve inside the ecosystems of our bodies. We describe how microbe-cancer cell interactions contribute to cancer progression, including cooperation between microbes and cancer cells. We discuss the role of the immune system in preventing this apparent 'collusion' and describe how microbe-cancer cell interactions lead to opportunities and challenges in treating cancer. RECENT FINDINGS Microbiota influence many aspects of our health including our cancer risk. Since both microbes and cancer cells rely on incoming resources for their survival and replication, excess energy and nutrient input from the host can play a role in cancer initiation and progression. Certain microbes enhance cancer cell fitness by promoting proliferation and protecting cancer cells from the immune system. How diet influences these interactions remains largely unknown but recent evidence suggests a role for nutrients across the cancer continuum.
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Affiliation(s)
- Corrie M Whisner
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
| | - C Athena Aktipis
- Department of Psychology, Center for Social Dynamics and Complexity, Center for Evolution and Medicine, Biodesign Institute, Arizona State University, PO Box 871104, Tempe, AZ, 85287-1104, USA.
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Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma. Eur J Nutr 2019; 59:557-569. [PMID: 30762097 PMCID: PMC7058602 DOI: 10.1007/s00394-019-01925-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 02/05/2019] [Indexed: 12/19/2022]
Abstract
Objective(s) Isothiocyanates (ITCs) are biologically active plant secondary metabolites capable of mediating various biological effects including modulation of the epigenome. Our aim was to characterize the effect of allyl isothiocyanate (AITC) on lysine acetylation and methylation marks as a potential epigenetic-induced anti-melanoma strategy. Methods Our malignant melanoma model consisted of (1) human (A375) and murine (B16-F10) malignant melanoma as well as of human; (2) brain (VMM1) and lymph node (Hs 294T) metastatic melanoma; (3) non-melanoma epidermoid carcinoma (A431) and (4) immortalized keratinocyte (HaCaT) cells subjected to AITC. Cell viability, histone deacetylases (HDACs) and acetyltransferases (HATs) activities were evaluated by the Alamar blue, Epigenase HDAC Activity/Inhibition and EpiQuik HAT Activity/Inhibition assay kits, respectively, while their expression levels together with those of lysine acetylation and methylation marks by western immunoblotting. Finally, apoptotic gene expression was assessed by an RT-PCR-based gene expression profiling methodology. Results AITC reduces cell viability, decreases HDACs and HATs activities and causes changes in protein expression levels of various HDACs, HATs, and histone methyl transferases (HMTs) all of which have a profound effect on specific lysine acetylation and methylation marks. Moreover, AITC regulates the expression of a number of genes participating in various apoptotic cascades thus indicating its involvement in apoptotic induction. Conclusions AITC exerts a potent epigenetic effect suggesting its potential involvement as a promising epigenetic-induced bioactive for the treatment of malignant melanoma.
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Aksornthong C, Prutipanlai S, Ruangrut P, Janchawee B. Cooking has the potential to decrease the antitumor effect of fresh Betong watercress. J Food Biochem 2019; 43:e12783. [PMID: 31353578 DOI: 10.1111/jfbc.12783] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 12/04/2018] [Accepted: 01/03/2019] [Indexed: 11/28/2022]
Abstract
Betong watercress (Nasturtium officinale R.Br.) contains phenethyl isothiocyanate (PEITC), derived from myrosinase-mediated hydrolysis of glucosinolates. Effects of fresh and cooked Betong watercress (FBW & CBW) on N-demethylation and C-8-hydroxylation of caffeine (CF) in rats were investigated. Wistar rats received a single dose of CF before and after pretreatments with a single or five-day administration of PEITC, FBW, and CBW dry powders. Plasma CF metabolic ratios (CMRs) were compared between before and after pretreatments. Single pretreatment with PEITC, FBW, but not CBW, significantly decreased CMRs. Five-day pretreatment with PEITC, FBW, and CBW significantly decreased CMRs. The decreases in CMRs after multiple doses of PEITC, FBW, and CBW were significantly higher than after a single dose. The decrease in CMRs caused by CBW was significantly lower than those by FBW, both single- and multiple doses. Cooking decreases the activity of FBW in inhibition of CYP1A2 mediating CF metabolism. PRACTICAL APPLICATIONS: PEITC and fresh watercress possess chemoprotective effects due to the inhibitory activity of PEITC on cytochrome P450s mediated bioactivation of carcinogens. Several clinical trials of the therapeutic uses of PEITC for cancer and other diseases are still in the pipeline. Betong watercress is a common ingredient in hot soup and stir-fried Thai recipes. Cooking heat inactivates plant myrosinase involving the production of PEITC. Consumption of watercress in cooked form may contribute less chemoprotective benefit. More appropriate preparation to deliver PEITC is needed to be evaluated.
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Affiliation(s)
- Chunhajan Aksornthong
- Faculty of Science, Department of Pharmacology, Prince of Songkla University, Songkhla, Thailand
| | - Sathaporn Prutipanlai
- Faculty of Science, Department of Pharmacology, Prince of Songkla University, Songkhla, Thailand
| | - Pritsana Ruangrut
- Faculty of Medicine, Department of Biomedical Sciences, Prince of Songkla University, Songkhla, Thailand
| | - Benjamas Janchawee
- Faculty of Science, Department of Pharmacology, Prince of Songkla University, Songkhla, Thailand
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Mitsiogianni M, Amery T, Franco R, Zoumpourlis V, Pappa A, Panayiotidis MI. From chemo-prevention to epigenetic regulation: The role of isothiocyanates in skin cancer prevention. Pharmacol Ther 2018; 190:187-201. [DOI: 10.1016/j.pharmthera.2018.06.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Wang C, Shu L, Zhang C, Li W, Wu R, Guo Y, Yang Y, Kong AN. Histone Methyltransferase Setd7 Regulates Nrf2 Signaling Pathway by Phenethyl Isothiocyanate and Ursolic Acid in Human Prostate Cancer Cells. Mol Nutr Food Res 2018; 62:e1700840. [PMID: 29383876 PMCID: PMC6226019 DOI: 10.1002/mnfr.201700840] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 12/08/2017] [Indexed: 01/05/2023]
Abstract
SCOPE This study aims to investigate the role of the epigenetic regulator SET domain-containing lysine methyltransferase 7 (Setd7) in regulating the antioxidant Nrf2 pathway in prostate cancer (PCa) cells and examines the effects of two phytochemicals, phenethyl isothiocyanate (PEITC) and ursolic acid (UA). METHODS AND RESULTS Lentivirus-mediated shRNA knockdown of Setd7 in LNCaP and PC-3 cells decreases the expression of downstream Nrf2 targets, such as NAD(P)H: quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase theta 2 (Gstt2). Downregulation of Setd7 decreases soft agar colony formation ability of PCa cells. Knockdown of Setd7 increases reactive oxygen species (ROS) generation. Furthermore, Setd7 knockdown attenuates Nqo1 and Gstt2 expression in response to H2 O2 challenge, whereas increased DNA damage is observed in Setd7 knockdown cells in comet assay. Interestingly, Setd7 expression could be induced by the dietary phytochemicals PEITC and UA. Chromatin immunoprecipitation (ChIP) assays show that Setd7 knockdown decreased H3K4me1 enrichment in the Nrf2 and Gstt2 promoter regions, while PEITC and UA treatments elevated the enrichment. CONCLUSION Taken together, these results indicate that Setd7 knockdown decreases Nrf2 and Nrf2-target genes expression and that PEITC and UA induce Setd7 expression, which activates the Nrf2/antioxidant response element (ARE) signaling pathway and protects DNA from oxidative damage.
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Affiliation(s)
- Chao Wang
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Limin Shu
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Chengyue Zhang
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Wenji Li
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Renyi Wu
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Yue Guo
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Yuqing Yang
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
| | - Ah-Ng Kong
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
- Center for Phytochemical Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, USA
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Arumugam A, Abdull Razis AF. Apoptosis as a Mechanism of the Cancer Chemopreventive Activity of Glucosinolates: a Review. Asian Pac J Cancer Prev 2018; 19:1439-1448. [PMID: 29936713 PMCID: PMC6103590 DOI: 10.22034/apjcp.2018.19.6.1439] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 05/29/2018] [Indexed: 01/27/2023] Open
Abstract
Cruciferous vegetables are a rich source of glucosinolates that have established anti-carcinogenic activity. Naturally-occurring glucosinolates and their derivative isothiocyanates (ITCs), generated as a result of their enzymatic degradation catalysed by myrosinase, have been linked to low cancer incidence in epidemiological studies, and in animal models isothiocyanates suppressed chemically-induced tumorigenesis. The prospective effect of isothiocyanates as anti-carcinogenic agent has been much explored as cytotoxic against wide array of cancer cell lines and being explored for the development of new anticancer drugs. However, the mechanisms of isothiocyanates in inducing apoptosis against tumor cell lines are still largely disregarded. A number of mechanisms are believed to be involved in the glucosinolate-induced suppression of carcinogenesis, including the induction of apoptosis, biotransformation of xenobiotic metabolism, oxidative stress, alteration of caspase activity, angiogenesis, histone deacytylation and cell cycle arrest. The molecular mechanisms through which isothiocyanates stimulate apoptosis in cancer cell lines have not so far been clearly defined. This review summarizes the underlying mechanisms through which isothiocyanates modify the apoptotic pathway leading to cell death.
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Affiliation(s)
- Asvinidevi Arumugam
- Laboratory of UPM-MAKNA Cancer Research, Institute of Bioscience, University Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia.
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Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:5438179. [PMID: 29977456 PMCID: PMC6011061 DOI: 10.1155/2018/5438179] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/27/2018] [Accepted: 05/08/2018] [Indexed: 12/21/2022]
Abstract
Sulforaphane (SFN), a compound derived from cruciferous vegetables that has been shown to be safe and nontoxic, with minimal/no side effects, has been extensively studied due to its numerous bioactivities, such as anticancer and antioxidant activities. SFN exerts its anticancer effects by modulating key signaling pathways and genes involved in the induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis. SFN also upregulates a series of cytoprotective genes by activating nuclear factor erythroid-2- (NF-E2-) related factor 2 (Nrf2), a critical transcription factor activated in response to oxidative stress; Nrf2 activation is also involved in the cancer-preventive effects of SFN. Accumulating evidence supports that epigenetic modification is an important factor in carcinogenesis and cancer progression, as epigenetic alterations often contribute to the inhibition of tumor-suppressor genes and the activation of oncogenes, which enables cells to acquire cancer-promoting properties. Studies on the mechanisms underlying the anticancer effects of SFN have shown that SFN can reverse such epigenetic alterations in cancers by targeting DNA methyltransferases (DNMTs), histone deacetyltransferases (HDACs), and noncoding RNAs. Therefore, in this review, we will discuss the anticancer activities of SFN and its mechanisms, with a particular emphasis on epigenetic modifications, including epigenetic reactivation of Nrf2.
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48
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Glucosinolate and isothiocyanate intakes are inversely associated with breast cancer risk: a case–control study in China. Br J Nutr 2018; 119:957-964. [DOI: 10.1017/s0007114518000600] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
AbstractAlthough previous studies have investigated the association of cruciferous vegetable consumption with breast cancer risk, few studies focused on the association between bioactive components in cruciferous vegetables, glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This study aimed to examine the association between consumption of cruciferous vegetables and breast cancer risk according to GSL and ITC contents in a Chinese population. A total of 1485 cases and 1506 controls were recruited into this case–control study from June 2007 to March 2017. Consumption of cruciferous vegetables was assessed using a validated FFQ. Dietary GSL and ITC were computed by using two food composition databases linking GSL and ITC contents in cruciferous vegetables with responses to the FFQ. The OR and 95 % CI were assessed by unconditional logistic regression after adjusting for the potential confounders. Significant inverse associations were found between consumption of cruciferous vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the highest with the lowest quartile were 0·51 (95 % CI 0·41, 0·63) for cruciferous vegetables, 0·54 (95 % CI 0·44, 0·67) for GSL and 0·62 (95 % CI 0·50, 0·76) for ITC, respectively. These inverse associations were also observed in both premenopausal and postmenopausal women. Subgroup analysis by hormone receptor status found inverse associations between cruciferous vegetables, GSL and ITC and both hormone-receptor-positive or hormone-receptor-negative breast cancer. This study indicated that consumption of cruciferous vegetables, GSL and ITC was inversely associated with breast cancer risk among Chinese women.
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Vrhovac Madunić I, Madunić J, Antunović M, Paradžik M, Garaj-Vrhovac V, Breljak D, Marijanović I, Gajski G. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn Schmiedebergs Arch Pharmacol 2018. [PMID: 29541820 DOI: 10.1007/s00210-018-1486-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Apigenin is found in several dietary plant foods such as vegetables and fruits. To investigate potential anticancer properties of apigenin on human breast cancer, ER-positive MCF-7 and triple-negative MDA MB-231 cells were used. Moreover, toxicological safety of apigenin towards normal cells was evaluated in human lymphocytes. Cytotoxicity of apigenin towards cancer cells was evaluated by MTT assay whereas further genotoxic and oxidative stress parameters were measured by comet and lipid peroxidation assays, respectively. In order to examine the type of cell death induced by apigenin, several biomarkers were used. Toxicological safety towards normal cells was evaluated by cell viability and comet assays. After the treatment with apigenin, we observed changes in cell morphology in a dose- (10 to 100 μM) and time-dependent manner. Moreover, apigenin caused cell death in both cell lines leading to significant toxicity and dominantly to apoptosis. Furthermore, apigenin proved to be genotoxic towards the selected cancer cells with a potential to induce oxidative damage to lipids. Of great importance is that no significant cytogenotoxic effects were detected in normal cells. The observed cytogenotoxic and pro-cell death activities of apigenin coupled with its low toxicity towards normal cells indicate that this natural product could be used as a future anticancer modality. Therefore, further analysis to determine the exact mechanism of action and in vivo studies on animal models are warranted.
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Affiliation(s)
- Ivana Vrhovac Madunić
- Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia
| | - Josip Madunić
- Department of Molecular Biology, Faculty of Science, University of Zagreb, Horvatovac 102a/2, 10000, Zagreb, Croatia
| | - Maja Antunović
- Department of Molecular Biology, Faculty of Science, University of Zagreb, Horvatovac 102a/2, 10000, Zagreb, Croatia
| | - Mladen Paradžik
- Laboratory for Cell Biology and Signalling, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia
| | - Vera Garaj-Vrhovac
- Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia
| | - Davorka Breljak
- Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia
| | - Inga Marijanović
- Department of Molecular Biology, Faculty of Science, University of Zagreb, Horvatovac 102a/2, 10000, Zagreb, Croatia
| | - Goran Gajski
- Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
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50
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Yang M, Wang H, Zhou M, Liu W, Kuang P, Liang H, Yuan Q. The natural compound sulforaphene, as a novel anticancer reagent, targeting PI3K-AKT signaling pathway in lung cancer. Oncotarget 2018; 7:76656-76666. [PMID: 27765931 PMCID: PMC5363538 DOI: 10.18632/oncotarget.12307] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 09/12/2016] [Indexed: 11/25/2022] Open
Abstract
Lung cancer is one of the leading causes of cancer death worldwide. Isothiocyanates from cruciferous vegetables been shown to possess anticarcinogenic activities in lung malignances. We previously found sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), one new kind of isothiocyanates, existing in a relative high abundance in radish seeds. An efficient methodology based on macroporous resin and preparative high-performance liquid chromatography was developed to isolate SFE in reasonably large quantities, high purity and low cost. However, it is still largely unclear whether SFE could function as an antineoplastic compound, especially in lung cancer. In this study, we systematically investigated the anti-cancer effects of SFE in vitro as well as its possible underling molecular mechanisms in lung cancer. The acute toxicity tests and pharmacokinetics tests for SFE were performed to evaluate its drugability in mice. Also, we evaluated the in vivo anti-cancer effects of SFE using nude Balb/C mice with lung cancer xenograft. SFE can induce apoptosis of multiple lung cancer celllines and, thus, inhibited cancer cell proliferation. Lung cancer cells treated with SFE exhibit significant inhibition of the PI3K-AKT signaling pathway, including depressed PTEN expression and inhibition of AKT phosphoralation. At well-tolerated doses, administration of SFE to mice bearing lung cancer xenografts leads to significant inhibitions of tumor growth. In summary, our work identifies SFE as a novel natural broad-spectrum small molecule inhibitor for lung cancer.
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Affiliation(s)
- Ming Yang
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Haiyong Wang
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Mo Zhou
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Weilin Liu
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Pengqun Kuang
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Hao Liang
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Qipeng Yuan
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
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