Search

Your search keyword '"Csonka, Tamás"' showing total 2 results
Start Over Author "Csonka, Tamás" Topic oxidative stress
2 results on '"Csonka, Tamás"'

1. Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer

Author

Kovács, Patrik, Csonka, Tamás, Kovács, Tünde, Sári, Zsanett, Ujlaki, Gyula, Sipos, Adrien, Karányi, Zsolt, Szeőcs, Dóra, Hegedűs, Csaba, Uray, Karen, Jankó, Laura, Kiss, Máté, Kiss, Borbála, Laoui, Damya, Virág, László, Méhes, Gábor, Bai, Péter, Mikó, Edit, Faculty of Sciences and Bioengineering Sciences, Department of Bio-engineering Sciences, and Cellular and Molecular Immunology

Subjects
iNOS, breast cancer, lithocholic acid, oxidative stress, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article, peroxynitrite, 4HNE, NRF2
Abstract

In breast cancer patients, the diversity of the microbiome decreases, coinciding with decreased production of cytostatic bacterial metabolites like lithocholic acid (LCA). We hypothesized that LCA can modulate oxidative stress to exert cytostatic effects in breast cancer cells. Treatment of breast cancer cells with LCA decreased nuclear factor-2 (NRF2) expression and increased Kelch-like ECH associating protein 1 (KEAP1) expression via activation of Takeda G-protein coupled receptor (TGR5) and constitutive androstane receptor (CAR). Altered NRF2 and KEAP1 expression subsequently led to decreased expression of glutathione peroxidase 3 (GPX3), an antioxidant enzyme, and increased expression of inducible nitric oxide synthase (iNOS). The imbalance between the pro- and antioxidant enzymes increased cytostatic effects via increased levels of lipid and protein oxidation. These effects were reversed by the pharmacological induction of NRF2 with RA839, tBHQ, or by thiol antioxidants. The expression of key components of the LCA-elicited cytostatic pathway (iNOS and 4HNE) gradually decreased as the breast cancer stage advanced. The level of lipid peroxidation in tumors negatively correlated with the mitotic index. The overexpression of iNOS, nNOS, CAR, KEAP1, NOX4, and TGR5 or the downregulation of NRF2 correlated with better survival in breast cancer patients, except for triple negative cases. Taken together, LCA, a metabolite of the gut microbiome, elicits oxidative stress that slows down the proliferation of breast cancer cells. The LCA&ndash, oxidative stress protective pathway is lost as breast cancer progresses, and the loss correlates with poor prognosis.

Published
2019

2. Indolepropionic Acid, a Metabolite of the Microbiome, Has Cytostatic Properties in Breast Cancer by Activating AHR and PXR Receptors and Inducing Oxidative Stress.

Author

Sári, Zsanett, Mikó, Edit, Kovács, Tünde, Jankó, Laura, Csonka, Tamás, Lente, Gréta, Sebő, Éva, Tóth, Judit, Tóth, Dezső, Árkosy, Péter, Boratkó, Anita, Ujlaki, Gyula, Török, Miklós, Kovács, Ilona, Szabó, Judit, Kiss, Borbála, Méhes, Gábor, Goedert, James J., and Bai, Péter

Subjects
CELL proliferation, ANIMAL experimentation, ANTINEOPLASTIC agents, BREAST tumors, CELL differentiation, CELL lines, CELL receptors, CELL motility, DIETARY supplements, IMMUNITY, METABOLITES, METASTASIS, MICE, STEM cells, TRYPTOPHAN, NITRIC-oxide synthases, GUT microbiome, OXIDATIVE stress, PHARMACODYNAMICS
Abstract

Oncobiotic transformation of the gut microbiome may contribute to the risk of breast cancer. Recent studies have provided evidence that the microbiome secretes cytostatic metabolites that inhibit the proliferation, movement, and metastasis formation of cancer cells. In this study, we show that indolepropionic acid (IPA), a bacterial tryptophan metabolite, has cytostatic properties. IPA selectively targeted breast cancer cells, but it had no effects on non-transformed, primary fibroblasts. In cell-based and animal experiments, we showed that IPA supplementation reduced the proportions of cancer stem cells and the proliferation, movement, and metastasis formation of cancer cells. These were achieved through inhibiting epithelial-to-mesenchymal transition, inducing oxidative and nitrosative stress, and boosting antitumor immune response. Increased oxidative/nitrosative stress was due to the IPA-mediated downregulation of nuclear factor erythroid 2-related factor 2 (NRF2), upregulation of inducible nitric oxide synthase (iNOS), and enhanced mitochondrial reactive species production. Increased oxidative/nitrosative stress led to cytostasis and reductions in cancer cell stem-ness. IPA exerted its effects through aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR) receptors. A higher expression of PXR and AHR supported better survival in human breast cancer patients, highlighting the importance of IPA-elicited pathways in cytostasis in breast cancer. Furthermore, AHR activation and PXR expression related inversely to cancer cell proliferation level and to the stage and grade of the tumor. The fecal microbiome's capacity for IPA biosynthesis was suppressed in women newly diagnosed with breast cancer, especially with stage 0. Bacterial indole biosynthesis showed correlation with lymphocyte infiltration to tumors in humans. Taken together, we found that IPA is a cytostatic bacterial metabolite, the production of which is suppressed in human breast cancer. Bacterial metabolites, among them, IPA, have a pivotal role in regulating the progression but not the initiation of the disease. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results