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Yang J, Zhang K, Shi J, Li Z, Dai H, Yang W. Perfluoroalkyl and polyfluoroalkyl substances and Cancer risk: results from a dose-response Meta-analysis. JOURNAL OF ENVIRONMENTAL HEALTH SCIENCE & ENGINEERING 2024; 22:455-469. [PMID: 39464822 PMCID: PMC11499464 DOI: 10.1007/s40201-024-00899-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 03/06/2024] [Indexed: 10/29/2024]
Abstract
Background Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent organic pollutants in the environment. While some studies suggest that PFASs may contribute to cancer development, the link between PFAS exposure and cancer risk remains debated. Methods This dose-response meta-analysis explores the relationship between PFASs and cancer. It employs odds ratio (OR) and standardized mean difference (SMD), along with their 95% confidence interval (CI), to assess the effects of PFASs on cancer risk. Relevant studies were sourced from Web of Science, PubMed, Embase, Medline, and CNKI databases. The dose-response relationship was assessed by the fixed-effects model and least-squares regression. Results Forty studies, involving a total of 748,188 participants, were included in this meta-analysis. Out of these, 13 studies were specifically analyzed for the dose-response relationship. Findings revealed that exposure to PFASs, especially PFDA, significantly raises the risk of genitourinary cancers, and PFDA exposure shows a dose-dependent increase in overall and breast cancer risk. Additionally, PFOS exposure is associated with an increased cancer risk, and elevated PFOA levels were significantly observed in breast cancer patients. Conclusions The findings suggest that PFAS exposure is a potential cancer risk factor, with the carcinogenic potential of PFDA being dose-dependent. Supplementary Information The online version contains supplementary material available at 10.1007/s40201-024-00899-w.
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Affiliation(s)
- Jingxuan Yang
- Department of Physiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041 People’s Republic of China
| | - Kui Zhang
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041 People’s Republic of China
| | - Jingyi Shi
- Department of Physiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041 People’s Republic of China
| | - Zhuo Li
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041 People’s Republic of China
| | - Hao Dai
- Department of Forensic Pathology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041 People’s Republic of China
| | - Wenxing Yang
- Department of Physiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041 People’s Republic of China
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Liu MM, Zhu HH, Bai J, Tian ZY, Zhao YJ, Boekhout T, Wang QM. Breast cancer colonization by Malassezia globosa accelerates tumor growth. mBio 2024; 15:e0199324. [PMID: 39235230 PMCID: PMC11481877 DOI: 10.1128/mbio.01993-24] [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: 07/02/2024] [Accepted: 07/18/2024] [Indexed: 09/06/2024] Open
Abstract
Malassezia globosa is a lipophilic basidiomycetous yeast that occurs abundantly in breast tumors and that may contribute to a shortened overall survival of breast cancer (BRAC) patients, suggesting that the yeast may participate in the carcinogenesis of BRAC. However, the mechanisms involved in the M. globosa-based acceleration of BRAC are unknown. Here, we show that M. globosa can colonize mammary tissue in 7,12-dimethylbenz[a] anthracene-induced mice. The abundance of M. globosa shortened the overall survival and increased the tumor incidence. Transcriptome data illustrated that IL-17A plays a key role in tumor growth due to M. globosa colonization, and tumor-associated macrophage infiltration was elevated during M. globosa colonization which triggers M2 polarization of macrophages via toll-like receptors 4/nuclear factor kappa-B (Nf-κB) signaling. Our results show that the expression of sphingosine kinase 1 (Sphk1) is increased in breast tumors after inoculation with M. globosa. Moreover, we discovered that Sphk1-specific small interfering RNA blocked the formation of lipid droplets, which can effectively alleviate the expression of the signal transducer and activator of the transcription 3 (STAT3)/Nf-κB pathway. Taken together, our results demonstrate that M. globosa could be a possible factor for the progression of BRAC. The mechanisms by which M. globosa promotes BRAC development involve the IL-17A/macrophage axis. Meanwhile, Sphk1 overexpression was induced by M. globosa infection, which also promoted the proliferation of MCF-7 cells.IMPORTANCELiterature has suggested that Malassezia globosa is associated with breast tumors; however, this association has not been confirmed. Here, we found that M. globosa colonizes in breast fat pads leading to tumor growth. As a lipophilic yeast, the expression of sphingosine kinase 1 (Sphk1) was upregulated to promote tumor growth after M. globosa colonization. Moreover, the IL-17A/macrophages axis plays a key role in mechanisms involved in the M. globosa-induced breast cancer acceleration from the tumor immune microenvironment perspective.
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Affiliation(s)
- Miao-Miao Liu
- School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China
| | - Hui-Hui Zhu
- School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China
| | - Jie Bai
- School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China
| | - Zi-Ye Tian
- School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China
| | - Yu-Jing Zhao
- School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China
| | - Teun Boekhout
- College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Qi-Ming Wang
- School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, Hebei, China
- Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding, Hebei, China
- Engineering Research Center of Ecological Safety and Conservation in Beijing-Tianjin-Hebei (Xiong’an New Area) of MOE, Xiong’an, China
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Attah CO, Alhaji UI, Ameh DA, Forcados GE, Muhammad A, Bashir M, Ibrahim S. In Vivo Chemosuppressive Effects of Kolaviron on 7,12-Dimethylbenzanthracene-Induced Mammary Lesions are Associated with Changes in Levels of Estrogen Receptor-α, CYP 1A1, Proinflammatory Cytokines, and Alterations to Metabolic Pathways Implicated in Mammary Carcinogenesis. J Med Food 2024; 27:940-950. [PMID: 39093123 DOI: 10.1089/jmf.2023.0158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024] Open
Abstract
Garcinia kola is a medicinal food commonly consumed in Sub-Sahara Africa, for which Kolaviron (KV) is the active portion. As a follow-up to our earlier chemopreventive studies, we investigated the chemotherapeutic effects of KV on experimentally induced mammary carcinogenesis in female Wistar rats. Mammary carcinogenesis was induced using 80 mg/kg of 7,12-dimethylbenzanthracene (DMBA) administered by oral gavage. One hundred-fifty days post-DMBA induction, estrogen receptor-α (ER-α) levels were determined in the experimental rats before treatment with KV commenced. Treatment was done using 50, 100, and 200 mg/kg KV thrice a week for 4 weeks, after which the experiment was terminated. Significantly higher levels of estrogen receptor-α, CYP 1A1, malondialdehyde, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased cytokine (interleukin-6 and tumor necrosis factor-α) activity were observed in DMBA-induced rats, which were attenuated in KV-treated rats. Tyrosine metabolism was exclusively enriched in DMBA-induced rats in contrast to KV-treated rats. Collectively, the results point to the chemotherapeutic potential of KV.
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Affiliation(s)
- Catherine Ojebbah Attah
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | - Umar Ismail Alhaji
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | - Danladi Amodu Ameh
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | | | - Aliyu Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
| | - Musa Bashir
- Center for Dryland Agriculture, Bayero University, Kano, Nigeria
| | - Sani Ibrahim
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University Zaria, Zaria, Nigeria
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Zakic T, Pekovic-Vaughan V, Cvoro A, Korac A, Jankovic A, Korac B. Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. FEBS Lett 2024; 598:2106-2134. [PMID: 38140817 DOI: 10.1002/1873-3468.14794] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/06/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023]
Abstract
Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.
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Affiliation(s)
- Tamara Zakic
- Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, Serbia
| | - Vanja Pekovic-Vaughan
- Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, William Henry Duncan Building, University of Liverpool, UK
| | | | | | - Aleksandra Jankovic
- Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, Serbia
| | - Bato Korac
- Institute for Biological Research "Sinisa Stankovic"-National Institute of Republic of Serbia, University of Belgrade, Serbia
- Faculty of Biology, University of Belgrade, Serbia
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Improta-Caria AC, Ferrari F, Gomes JLP, Villalta PB, Soci ÚPR, Stein R, Oliveira EM. Dysregulated microRNAs in type 2 diabetes and breast cancer: Potential associated molecular mechanisms. World J Diabetes 2024; 15:1187-1198. [PMID: 38983808 PMCID: PMC11229979 DOI: 10.4239/wjd.v15.i6.1187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 03/03/2024] [Accepted: 04/26/2024] [Indexed: 06/11/2024] Open
Abstract
Type 2 diabetes (T2D) is a multifaceted and heterogeneous syndrome associated with complications such as hypertension, coronary artery disease, and notably, breast cancer (BC). The connection between T2D and BC is established through processes that involve insulin resistance, inflammation and other factors. Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC, especially through microRNAs (miRNAs), remain elusive. miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes. However, the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated. This review aims to identify dysregulated miRNAs in both T2D and BC, exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.
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Affiliation(s)
- Alex Cleber Improta-Caria
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo 05508-030, Brazil
| | - Filipe Ferrari
- Graduate Program in Cardiology and Cardiovascular Sciences, Federal University of Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035003, Brazil
| | - João Lucas Penteado Gomes
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo 05508-030, Brazil
| | - Paloma Brasilio Villalta
- Laboratory of Metabolic Disorders (Labdime), School of Applied Sciences, University of Campinas-UNICAMP, Campinas 13484-350, Brazil
| | - Úrsula Paula Renó Soci
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo 05508-030, Brazil
| | - Ricardo Stein
- Graduate Program in Cardiology and Cardiovascular Sciences, Federal University of Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035003, Brazil
| | - Edilamar M Oliveira
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo 05508-030, Brazil
- Departments of Internal Medicine, Molecular Pharmacology and Physiology, Center for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, United States
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Sarf EA, Dyachenko EI, Bel’skaya LV. The Role of Salivary Vascular Endothelial Growth Factor A, Cytokines, and Amino Acids in Immunomodulation and Angiogenesis in Breast Cancer. Biomedicines 2024; 12:1329. [PMID: 38927536 PMCID: PMC11201966 DOI: 10.3390/biomedicines12061329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 06/13/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024] Open
Abstract
In this work, we focused on the analysis of VEGF content in saliva and its relationship with pro-inflammatory cytokines and amino acids involved in immunomodulation and angiogenesis in breast cancer. The study included 230 breast cancer patients, 92 patients with benign breast disease, and 59 healthy controls. Before treatment, saliva samples were obtained from all participants, and the content of VEGF and cytokines in saliva was determined by an enzyme-linked immunosorbent assay, as well as the content of amino acids by high-performance liquid chromatography. It was found that VEGF was positively correlated with the level of pro-inflammatory cytokines IL-1β (r = 0.6367), IL-6 (r = 0.3813), IL-8 (r = 0.4370), and IL-18 (r = 0.4184). Weak correlations were shown for MCP-1 (r = 0.2663) and TNF-α (r = 0.2817). For the first time, we demonstrated changes in the concentration of VEGF and related cytokines in saliva in different molecular biological subtypes of breast cancer depending on the stage of the disease, differentiation, proliferation, and metastasis to the lymph nodes. A correlation was established between the expression of VEGF and the content of aspartic acid (r = -0.3050), citrulline (r = -0.2914), and tryptophan (r = 0.3382) in saliva. It has been suggested that aspartic acid and citrulline influence the expression of VEGF via the synthesis of the signaling molecule NO, and then tryptophan ensures tolerance of the immune system to tumor cells.
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Affiliation(s)
| | | | - Lyudmila V. Bel’skaya
- Biochemistry Research Laboratory, Omsk State Pedagogical University, 14, Tukhachevsky Str., 644099 Omsk, Russia; (E.A.S.); (E.I.D.)
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Mlinarić M, Lučić I, Tomljanović M, Tartaro Bujak I, Milković L, Čipak Gašparović A. AQP3 and AQP5 Modulation in Response to Prolonged Oxidative Stress in Breast Cancer Cell Lines. Antioxidants (Basel) 2024; 13:626. [PMID: 38929065 PMCID: PMC11200458 DOI: 10.3390/antiox13060626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/03/2024] [Accepted: 05/17/2024] [Indexed: 06/28/2024] Open
Abstract
Aquaporins are membrane pores regulating the transport of water, glycerol, and other small molecules across membranes. Among 13 human aquaporins, six have been shown to transport H2O2 and are therefore called peroxiporins. Peroxiporins are implicated in cancer development and progression, partly due to their involvement in H2O2 transport. Oxidative stress is linked to breast cancer development but is also a mechanism of action for conventional chemotherapy. The aim of this study is to investigate the effects of prolonged oxidative stress on Aquaporin 3 (AQP3), Aquaporin 5 (AQP5), and signaling pathways in breast cancer cell lines of different malignancies alongside a non-tumorigenic breast cell line. The prolonged oxidative stress caused responses in viability only in the cancer cell lines, while it affected cell migration in the MCF7 cell line. Changes in the localization of NRF2, a transcription factor involved in oxidative stress response, were observed only in the cancer cell lines, and no effects were recorded on its downstream target proteins. Moreover, the prolonged oxidative stress caused changes in AQP3 and AQP5 expression only in the cancer cell lines, in contrast to their non-malignant counterparts. These results suggest peroxiporins are potential therapeutic targets in cancer treatment. However, further research is needed to elucidate their role in the modulation of therapy response, highlighting the importance of research on this topic.
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Affiliation(s)
- Monika Mlinarić
- Laboratory for Membrane Transport and Signaling, Division of Molecular Medicine, Ruđer Bošković Institute, HR10000 Zagreb, Croatia; (M.M.); (I.L.); (M.T.); (L.M.)
| | - Ivan Lučić
- Laboratory for Membrane Transport and Signaling, Division of Molecular Medicine, Ruđer Bošković Institute, HR10000 Zagreb, Croatia; (M.M.); (I.L.); (M.T.); (L.M.)
| | - Marko Tomljanović
- Laboratory for Membrane Transport and Signaling, Division of Molecular Medicine, Ruđer Bošković Institute, HR10000 Zagreb, Croatia; (M.M.); (I.L.); (M.T.); (L.M.)
| | - Ivana Tartaro Bujak
- Radiation Chemistry and Dosimetry Laboratory, Division of Materials Chemistry, Ruđer Bošković Institute, HR10000 Zagreb, Croatia;
| | - Lidija Milković
- Laboratory for Membrane Transport and Signaling, Division of Molecular Medicine, Ruđer Bošković Institute, HR10000 Zagreb, Croatia; (M.M.); (I.L.); (M.T.); (L.M.)
| | - Ana Čipak Gašparović
- Laboratory for Membrane Transport and Signaling, Division of Molecular Medicine, Ruđer Bošković Institute, HR10000 Zagreb, Croatia; (M.M.); (I.L.); (M.T.); (L.M.)
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Correlation between oxidative stress markers and cytokines in different stages of breast cancer. Cytokine 2023; 161:156082. [PMID: 36347127 DOI: 10.1016/j.cyto.2022.156082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 10/17/2022] [Accepted: 10/26/2022] [Indexed: 11/08/2022]
Abstract
This study aims to estimate the level of malondialdehyde (MDA) as oxidative stress marker and reduced glutathione (GSH) as antioxidant and correlate them to different inflammatory markers as interleukins (IL-6, IL-8, IL-10) and tumor necrosis factor alpha (TNF-α) in different stages of breast cancer (BC). For the purpose of comparisons, 35 healthy subjects matched for age, sex and ethnic background were selected who have no history or clinical evidence of BC or any chronic disease and obvious abnormalities as a control group and 35 patients of different stages of BC were participated in the study. The cancer patients were diagnosed by specialists. Even the exact cause of the disease has not been identified but according to this study, 5% of the patients were having family history of the disease and 62% of the patients were having a BMI over 25. Over 60% of the patients were postmenopausal and all females participated in this study were nonsmokers. MDA level showed a significant increase when BC patients were compared to healthy subjects, this oxidative stress marker showed a significant increase with the increase of the stage of the disease. In contrast the level of the lipid peroxide scavenger GSH reduced with increasing the stage of the disease. The level of some cytokines showed a significant change between different stages and the control group. Correlation between MDA and GSH with these cytokines showed a positive correlation between all cytokines and the MDA level and a negative correlation between GSH and the cytokines. The results of this study suggests that BC stimulates the oxidative stress response and for that, different inflammatory cytokines will be produced and there is a pronounced relationship between oxidative stress parameters and these cytokines and the level of these cytokines are associated with aggressive tumors.
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Feng M, Wang H, Zhu Z, Yao B, Li Y, Xue J, Cao S, Shao X, Xu Y, Sohn KC, Shin IH, Yao C. Sanhuang Decoction Controls Tumor Microenvironment by Ameliorating Chronic Stress in Breast Cancer: A Report of Ninety Cases. Front Oncol 2021; 11:677939. [PMID: 34485118 PMCID: PMC8416106 DOI: 10.3389/fonc.2021.677939] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 07/27/2021] [Indexed: 01/18/2023] Open
Abstract
Long-term endocrine treatment which results in estrogen deprivation causes chronic stress associated with a series of uncomfortable symptoms leading not only to a decrease in quality of life but also to cancer recurrence, which may be mediated primarily through the enhanced expression of angiogenic factors, as well as a series of inflammatory microenvironmental changes that favor tumor progression. In this study, we designed a clinical trial and aimed to explore the effects of Sanhuang Decoction (SHD) treatment on chronic stress, inflammatory factors, and breast cancer recovery. A total of 90 patients with breast cancer who met the inclusion/exclusion criteria were randomly allocated to a treatment or control group. The treatment group received the standard endocrine treatment and the traditional Chinese medicine decoction known as SHD. The control group received the standard endocrine treatment only. The treatment period was 6 months. The modified Kupperman Menopausal Index, the self-rating anxiety scale, and the self-rating depression scale were evaluated once per month. The body microenvironment plasma indices related to chronic stress, such as oxidative and antioxidative stress markers, inflammatory factors, hemorheology, coagulation, lipid and D-dimer, immunologic functions, tumor biomarkers, and angiogenic factors of the vascular endothelial growth factor (VEGF) were measured before and after 6 months of treatment. After treatment for 5 months, the scores in the treatment group decreased to nearly normal levels and the control group showed no significant improvement. After treatment for 6 months, all indices related to the body microenvironment, as well as the tumor biomarkers and carcinoembryonic antigen, carbohydrate antigen 153, and angiogenic factor VEGF levels improved significantly to normal levels in the treatment group. Our primary research showed that treatment with SHD effectively improved the quality of life of breast cancer patients by facilitating a change in the body microenvironment that controlled tumor growth and prevented drug resistance.
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Affiliation(s)
- Ming Feng
- The First Clinical college, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Huanhuan Wang
- The First Clinical college, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhiyuan Zhu
- The First Clinical college, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Bowen Yao
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
| | - Yongfei Li
- Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jingxian Xue
- Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Sihan Cao
- The First Clinical college, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinyi Shao
- The First Clinical college, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanlei Xu
- Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Ki Cheul Sohn
- School of Medicine, Catholic University of Daegu, Gyeongsan, South Korea
| | - Im Hee Shin
- School of Medicine, Catholic University of Daegu, Gyeongsan, South Korea
| | - Chang Yao
- Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Nath M, Bhattacharjee K, Choudhury Y. Vildagliptin, a dipeptidyl peptidase-4 inhibitor, reduces betel-nut induced carcinogenesis in female mice. Life Sci 2020; 266:118870. [PMID: 33310040 DOI: 10.1016/j.lfs.2020.118870] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/11/2020] [Accepted: 12/01/2020] [Indexed: 12/27/2022]
Abstract
AIM Betel-nut, a popular masticatory among Southeast Asian populations is a class I carcinogen, previously associated with dyslipidemia and aberrant lipid metabolism, and is reported to be used more frequently by females, than males. This study investigates the potential of repurposing the anti-diabetic drug, vildagliptin, a dipeptidyl peptidase-4 inhibitor, for alleviating the oncogenic condition in female Swiss Albino mice administered an aqueous extract of betel-nut (AEBN) orally (2 mg ml-1) for 24 weeks. MAIN METHODS Tissues were investigated by histopathological, immunohistochemical and apoptosis assays. Biochemical analyses of oxidative stress markers and lipid profile were performed using different tissues and sera. The expressions of different proteins involved in lipid metabolism and oncogenic pathways were evaluated by Western blotting. KEY FINDINGS AEBN induced carcinogenesis primarily in the liver by significantly impairing AMPK signaling, inducing oxidative stress, activating Akt/mTOR signaling, increasing Ki-67 immunoreactivity and cyclin D1 expression, and significantly diminishing apoptosis. Co-administration of AEBN with vildagliptin (10 mg kg-1 body weight) for 8 weeks reduced liver dysplasia, and significantly decreased free palmitic acid, increased free oleic acid, normalized lipid profile, decreased oxidative stress, cyclin D1 expression, Ki-67 immunoreactivity, and Bcl2 expression, and increased the ratio of apoptotic/non-apoptotic cells. Mechanistically, vildagliptin elicited these physiological and molecular alterations by restoring normal AMPK signaling and reducing the cellular expressions of FASN and HMGCR, restoring AMPK-dependent phosphorylation of p53 at Ser-15 and reducing Akt/mTOR signaling. SIGNIFICANCE These results indicate that vildagliptin may alleviate betel-nut induced carcinogenesis in the liver of female mice.
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Affiliation(s)
- Moumita Nath
- Department of Biotechnology, Assam University, Silchar 788011, Assam, India
| | | | - Yashmin Choudhury
- Department of Biotechnology, Assam University, Silchar 788011, Assam, India.
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11
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Wu L, Fidan K, Um JY, Ahn KS. Telomerase: Key regulator of inflammation and cancer. Pharmacol Res 2020; 155:104726. [PMID: 32109579 DOI: 10.1016/j.phrs.2020.104726] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 02/24/2020] [Accepted: 02/24/2020] [Indexed: 12/11/2022]
Abstract
The telomerase holoenzyme, which has a highly conserved role in maintaining telomere length, has long been regarded as a high-profile target in cancer therapy due to the high dependency of the majority of cancer cells on constitutive and elevated telomerase activity for sustained proliferation and immortality. In this review, we present the salient findings in the telomerase field with special focus on the association of telomerase with inflammation and cancer. The elucidation of extra-telomeric roles of telomerase in inflammation, reactive oxygen species (ROS) generation, and cancer development further complicated the design of anti-telomerase therapy. Of note, the discovery of the unique mechanism that underlies reactivation of the dormant telomerase reverse transcriptase TERT promoter in somatic cells not only enhanced our understanding of the critical role of TERT in carcinogenesis but also opens up new intervention ideas that enable the differential targeting of cancer cells only. Despite significant effort invested in developing telomerase-targeted therapeutics, devising efficacious cancer-specific telomerase/TERT inhibitors remains an uphill task. The latest discoveries of the telomere-independent functionalities of telomerase in inflammation and cancer can help illuminate the path of developing specific anti-telomerase/TERT therapeutics against cancer cells.
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Affiliation(s)
- Lele Wu
- Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore 138673, Singapore
| | - Kerem Fidan
- Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 117597, Singapore
| | - Jae-Young Um
- College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, Dongdaemoon-gu, Seoul 130-701, Republic of Korea
| | - Kwang Seok Ahn
- College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
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12
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Silva AL, Faria M, Matos P. Inflammatory Microenvironment Modulation of Alternative Splicing in Cancer: A Way to Adapt. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1219:243-258. [PMID: 32130703 DOI: 10.1007/978-3-030-34025-4_13] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The relationship between inflammation and cancer has been long recognized by the medical and scientific community. In the last decades, it has returned to the forefront of clinical oncology since a wealth of knowledge has been gathered about the cells, cytokines and physiological processes that are central to both inflammation and cancer. It is now robustly established that chronic inflammation can induce certain cancers but also that solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination. Inflammation is the hallmark of the innate immune response to tissue damage or infection, but also mediates the activation, expansion and recruitment to the tissues of cells and antibodies of the adaptive immune system. The functional integration of both components of the immune response is crucial to identify and subdue tumor development, progression and dissemination. When this tight control goes awry, altered cells can avoid the immune surveillance and even subvert the innate immunity to promote their full oncogenic transformation. In this chapter, we make a general overview of the most recent data linking the inflammatory process to cancer. We start with the overall inflammatory cues and processes that influence the relationship between tumor and the microenvironment that surrounds it and follow the ever-increasing complexity of processes that end up producing subtle changes in the splicing of certain genes to ascertain survival advantage to cancer cells.
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Affiliation(s)
- Ana Luísa Silva
- Serviço de Endocrinologia, Diabetes e Metabolismo do CHLN-Hospital Santa Maria, Lisbon, Portugal
- ISAMB-Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Márcia Faria
- Serviço de Endocrinologia, Diabetes e Metabolismo do CHLN-Hospital Santa Maria, Lisbon, Portugal
- Faculdade de Ciências, BioISI-Biosystems and Integrative Sciences Institute, Universidade de Lisboa, Lisbon, Portugal
| | - Paulo Matos
- Faculdade de Ciências, BioISI-Biosystems and Integrative Sciences Institute, Universidade de Lisboa, Lisbon, Portugal
- Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
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El-Deeb MMK, El-Sheredy HG, Mohammed AF. The Possible Role of Interleukin (IL)-18 and Nitrous Oxide and Their Relation to Oxidative Stress in the Development and Progression of Breast Cancer. Asian Pac J Cancer Prev 2019; 20:2659-2665. [PMID: 31554361 PMCID: PMC6976825 DOI: 10.31557/apjcp.2019.20.9.2659] [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: 01/01/2019] [Indexed: 01/09/2023] Open
Abstract
Background: Cancer breast is the most common malignant tumor in females globally. Mechanisms linking inflammatory cytokines and tumour growth and progression have not been established. Interleukin (IL)-18 has a modifying role in the immune defense against tumor cells. It induces production of IFN-γ. It also increases the immune cells cytotoxic activity and enhances the production of other proinflammatory cytokine. Nitric oxide (NO) has both promoting and inhibiting effects on tumorigenesis. Oxidative stress is a phenomenon that leads to oxidative damage of biomolecules, mutagenesis and carcinogenesis. Objective: The purpose of this research is to identify the potential role of IL18 and NO and their relation to oxidative stress in the development of cancer breast. Patients and Methods: This study included 120 women split into two groups ; control group and patient groups that divided into: group B (30 patients with benign breast tumors), group N (30newly diagnosed cancer breast patients) ; and group M (30 metastatic cancer breast patients). Results: Serum total anti-oxidant capacity was significant high in both cancer breast groups. Total oxidative capacity was significantly higher level in metastatic group. NO levels were significantly higher values in the three cancer breast patients groups compared to control group.IL18 was significantly high in the metastatic group.
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Affiliation(s)
- Mona Mohamed K El-Deeb
- Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Heba Gaber El-Sheredy
- Department of Cancer Management and Research, Medical Research Institute, Alexandria University, Alexandria, Egypt.
| | - Ayman Farouk Mohammed
- Department of Surgery, Medical Research Institute, Alexandria University, Alexandria, Egypt
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14
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DNA damage and repair measured by comet assay in cancer patients. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2019; 843:95-110. [DOI: 10.1016/j.mrgentox.2019.05.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 05/14/2019] [Accepted: 05/18/2019] [Indexed: 02/08/2023]
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15
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Khadem-Ansari MH, Asoudeh M, Gheshlaghi HFK, Nozari S, Zarringol M, Maroufi NF, Faridvand Y. Copper and zinc in stage I multiple myeloma: relation with ceruloplasmin, lipid peroxidation, and superoxide dismutase activity. Horm Mol Biol Clin Investig 2018; 37:/j/hmbci.ahead-of-print/hmbci-2018-0055/hmbci-2018-0055.xml. [PMID: 30367794 DOI: 10.1515/hmbci-2018-0055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 09/11/2018] [Indexed: 11/15/2022]
Abstract
Background The main aim of this study was to assess the serum levels of copper (Cu), zinc (Zn) with lipid peroxidation, Cu/Zn superoxide dismutase (Cu/Zn SOD) activity, and ceruloplasmin (Cp) in multiple myeloma (MM) patients. Materials and methods The study was conducted in 34 MM patients at stage I. Serum Cu and Zn levels were measured by atomic absorption spectrometry. Also, spectrophotometric assays of malondialdehyde (MDA) levels in addition to Cp and Cu/Zn SOD were quantitated. Results The results showed a significant decrease in the serum Zn levels in patients with MM (p < 0.0001). Also, serum Cu levels were significantly higher (p < 0.0001). However, the serum Cu/Zn ratio was significantly higher in the cancer patients (p < 0.0001). A significant difference was observed in the patients group compared with the control group according to the Cu/Zn SOD activity (p < 0.0001). Moreover, serum levels of Cp and MDA were significantly increased in patients (p < 0.0001, both). Conclusions The elevated levels of serum Cu and MDA with a decrease in Zn and Cu/Zn SOD might explain the increased oxidative stress in MM disease. As the high Cu level was observed in MM patients, therefore, Cu levels should be concentrated in the pathogenesis and progression of MM disease.
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Affiliation(s)
| | - Mojtaba Asoudeh
- Department of Clinical Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | | | - Samira Nozari
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mina Zarringol
- Department of biochemistry, Islamic Azad University, Science and Research Branch, Tehran (Fars), Iran
| | - Nazila Fathi Maroufi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yousef Faridvand
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, Phone: +984432770698, Fax: +984432770698
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16
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Non-Clinical Studies for Evaluation of 8-C-Rhamnosyl Apigenin Purified from Peperomia obtusifolia against Acute Edema. Int J Mol Sci 2017; 18:ijms18091972. [PMID: 28906474 PMCID: PMC5618621 DOI: 10.3390/ijms18091972] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 09/09/2017] [Accepted: 09/09/2017] [Indexed: 01/02/2023] Open
Abstract
Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1β production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 μg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins.
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17
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Zhang DD, Zou MJ, Zhang YT, Fu WL, Xu T, Wang JX, Xia WR, Huang ZG, Gan XD, Zhu XM, Xu DG. A novel IL-1RA-PEP fusion protein with enhanced brain penetration ameliorates cerebral ischemia-reperfusion injury by inhibition of oxidative stress and neuroinflammation. Exp Neurol 2017; 297:1-13. [PMID: 28602833 DOI: 10.1016/j.expneurol.2017.06.012] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 05/14/2017] [Accepted: 06/07/2017] [Indexed: 12/21/2022]
Abstract
Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP). Studies were carried out in transient middle cerebral artery occlusion (MCAO) in rats and oxygen glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons. In MCAO rat model, IL-1RA-PEP (50mg/kg) injected i.v., penetrated BBB effectively, and alleviated brain infarction, cerebral edema, neurological deficit score and motor performance as well as inhibited the inflammatory cytokines expression. Furthermore, our results firstly showed that IL-1RA-PEP also regulated the oxidases expression, decreased the levels of NO, MDA and ROS. In addition, the inhibitory effects of IL-1RA-PEP on oxidative stress and inflammation were confirmed in rat cortical neurons induced by OGD/R, it reduced ROS, IL-6 and TNF-α. Further study showed that the effects of IL-1RA-PEP were closely associated with the NF-κB and p38 pathways which were proved respectively by their inhibitors JSH-23 and SB203580. Our results indicated that IL-1RA-PEP could effectively penetrate the brain of MCAO rats, alleviated the cerebral ischemia reperfusion injury by inhibiting neuroinflammation and oxidative stress, showing a great clinical potential for stroke.
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Affiliation(s)
- Dong-Dong Zhang
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China; Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China
| | - Min-Ji Zou
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Ya-Tao Zhang
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Wen-Liang Fu
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Tao Xu
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Jia-Xi Wang
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Wen-Rong Xia
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Zhi-Guang Huang
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Xiang-Dong Gan
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Xiao-Ming Zhu
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China
| | - Dong-Gang Xu
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China; Anhui Medical University, 81 Meishan Road, Hefei 230032, PR China.
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18
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Ci X, Zhou J, Lv H, Yu Q, Peng L, Hua S. Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism. Cell Death Dis 2017; 8:e2798. [PMID: 28518138 PMCID: PMC5520743 DOI: 10.1038/cddis.2017.39] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 01/11/2017] [Accepted: 01/12/2017] [Indexed: 12/14/2022]
Abstract
Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system. In macrophages, betulin activated the Nrf2 signaling pathway and increased Nrf2-targeted antioxidant and detoxifying enzymes, including NADPH, quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), γ-glutamyl cysteine synthetase catalytic subunit (GCLC) and modifier subunit (GCLM) in a dose and time dependent manner. Importantly, we found betulin-induced activation of Nrf2 is AMPK/AKT/GSK3β dependent, as pharmacologically inactivating AMPK blocked the activating effect of betulin on AKT, GSK3β and Nrf2. Furthermore, betulin attenuated LPS-induced inflammatory mediators (iNOS and COX-2) and MAPK inflammatory signaling pathway. The effect of betulin on HO-1 and NQO1 upregulation, iNOS and COX-2 the downregulation, and survival time extension was largely weakened when Nrf2 was depleted in vitro and in vivo. Our results demonstrate that the AMPK/AKT/Nrf2 pathways are essential for the anti-inflammatory effects of betulin in LPS-stimulated macrophages and endotoxin-shocked mice.
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Affiliation(s)
- Xinxin Ci
- Institute of Translational Medicine, Department of Respiratory Medicine, The First Hospital, Jilin University, Changchun 130001, China
| | - Junfeng Zhou
- Department of Dermatology and Venereology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Hongming Lv
- Institute of Translational Medicine, Department of Respiratory Medicine, The First Hospital, Jilin University, Changchun 130001, China
| | - Qinlei Yu
- Institute of Translational Medicine, Department of Respiratory Medicine, The First Hospital, Jilin University, Changchun 130001, China
| | - Liping Peng
- Institute of Translational Medicine, Department of Respiratory Medicine, The First Hospital, Jilin University, Changchun 130001, China
| | - Shucheng Hua
- Institute of Translational Medicine, Department of Respiratory Medicine, The First Hospital, Jilin University, Changchun 130001, China
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19
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Forcados GE, James DB, Sallau AB, Muhammad A, Mabeta P. Oxidative Stress and Carcinogenesis: Potential of Phytochemicals in Breast Cancer Therapy. Nutr Cancer 2017; 69:365-374. [PMID: 28103111 DOI: 10.1080/01635581.2017.1267777] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Breast cancer remains a burden in both developed and developing countries, with higher mortality in developing countries. Attempts to eradicate cancer have not been successful despite the progress made in the development of more novel chemotherapeutic drugs. Reactive-oxygen-species-mediated oxidative stress is known to play a role in breast cancer pathogenesis via genetic and epigenetic modifications, resulting in uncontrolled cell proliferation. Phytochemicals could provide leads for the development of alternative therapeutic agents due to their antioxidant activity, as well as their ability to induce apoptosis in cancer cells. However, most of the studies carried out using in vitro models do not continue with further studies in estrogen-receptor-positive in vivo breast cancer models, or fail to examine the possible biochemical mechanisms of phytochemical-based amelioration. This review examines oxidative-stress-mediated carcinogenesis and the potential of phytochemicals as anticancer agents.
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Affiliation(s)
- Gilead Ebiegberi Forcados
- a Division of Biochemistry , National Veterinary Research Institute , Vom , Nigeria.,b Department of Biochemistry , Faculty of Science, Ahmadu Bello University , Zaria , Nigeria.,c Department of Anatomy and Physiology , Faculty of Veterinary Sciences, University of Pretoria , Pretoria , South Africa
| | - Dorcas Bolanle James
- b Department of Biochemistry , Faculty of Science, Ahmadu Bello University , Zaria , Nigeria
| | | | - Aliyu Muhammad
- b Department of Biochemistry , Faculty of Science, Ahmadu Bello University , Zaria , Nigeria
| | - Peace Mabeta
- c Department of Anatomy and Physiology , Faculty of Veterinary Sciences, University of Pretoria , Pretoria , South Africa
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20
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Anuja K, Roy S, Ghosh C, Gupta P, Bhattacharjee S, Banerjee B. Prolonged inflammatory microenvironment is crucial for pro-neoplastic growth and genome instability: a detailed review. Inflamm Res 2016; 66:119-128. [PMID: 27653961 DOI: 10.1007/s00011-016-0985-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/25/2016] [Accepted: 08/31/2016] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Chronic inflammation can affect the normal cell homeostasis and metabolism by rendering the cells susceptible to genomic instability that may lead to uncontrolled cellular growth and proliferation ensuing tumorigenesis. The causal agents for inflammation may be pathogenic infections like microbial agents ranging from viruses to bacteria. These infections lead to DNA damage or disruption of normal cell metabolism and alter the genome integrity. FINDINGS In this review, we have highlighted the role of recurrent infections in tumor microenvironment can lead to recruitment of pro-inflammatory cells, cytokines and growth factors to the site of inflammation. This makes the environment rich in cytokines, chemokines, DNA-damaging agents (ROS, RNS) and growth factors which activate DNA damage response pathway and help in sustained proliferation of the tumor cells. In any inflammatory response, the production of cytokines and related signaling molecules is self-regulating and limiting. But in case of neoplastic risk, deregulation of these factors may lead to abnormalities and related pathogenesis. CONCLUSION The scope of the present review is to explore the probable mechanistic link and factors responsible for chronic inflammation. The relation between chronic inflammation and DNA damage response was further elucidated to understand the mechanism by which it makes the cells susceptible to carcinogenesis.
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Affiliation(s)
- Kumari Anuja
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India
| | - Souvick Roy
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India
| | - Chinmoy Ghosh
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India
| | - Priya Gupta
- Department of Molecular Biology and Bioinformatics, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India
| | - Surajit Bhattacharjee
- Department of Molecular Biology and Bioinformatics, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India.
| | - Birendranath Banerjee
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India.
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Wardill HR, Mander KA, Van Sebille YZA, Gibson RJ, Logan RM, Bowen JM, Sonis ST. Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction. Int J Cancer 2016; 139:2635-2645. [PMID: 27367824 DOI: 10.1002/ijc.30252] [Citation(s) in RCA: 109] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Accepted: 06/21/2016] [Indexed: 12/11/2022]
Abstract
Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity.
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Affiliation(s)
- Hannah R Wardill
- School of Medicine, University of Adelaide, South Australia. .,Centre for Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia.
| | - Kimberley A Mander
- School of Medicine, University of Adelaide, South Australia.,Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia
| | | | - Rachel J Gibson
- Division of Health Sciences, University of South Australia, Australia
| | - Richard M Logan
- School of Dentistry, University of Adelaide, Adelaide, South Australia
| | - Joanne M Bowen
- School of Medicine, University of Adelaide, South Australia
| | - Stephen T Sonis
- Brigham and Women's Hospital, Boston, MA.,Biomodels, LLC, Watertown, MA
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