Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness
| Autor: | Edit Mikó, Judit Szabó, Péter Bai, András Vida, Tünde Kovács, Zoltán Hujber, György Trencsényi, László Vígh, Anita Boratkó, Mitsuhiro Watanabe, Patrik Kovács, Borbála Kiss, Gyula Ujlaki, Gábor Méhes, James J. Goedert, Péter Antal-Szalmás, Tamás Csonka, Anna Sebestyén, Judit Márton, Balázs Csóka, Zsanett Sári, Imre Gombos |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lithocholic acid genetic structures medicine.drug_class Metabolite Detergents Biophysics Apoptosis Breast Neoplasms Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system Breast cancer Cell Movement Chenodeoxycholic acid medicine Tumor Cells Cultured Animals Humans Elméleti orvostudományok Cell Proliferation Mice Inbred BALB C Bile acid Bacteria Cell growth Orvostudományok Cell Biology Middle Aged medicine.disease Prognosis G protein-coupled bile acid receptor Xenograft Model Antitumor Assays 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research Female Lithocholic Acid |
| Zdroj: | Biochimica et biophysica acta. Bioenergetics. 1859(9) |
| ISSN: | 0005-2728 |
| Popis: | Our study aimed at finding a mechanistic relationship between the gut microbiome and breast cancer. Breast cancer cells are not in direct contact with these microbes, but disease could be influenced by bacterial metabolites including secondary bile acids that are exclusively synthesized by the microbiome and known to enter the human circulation. In murine and bench experiments, a secondary bile acid, lithocholic acid (LCA) in concentrations corresponding to its tissue reference concentrations (< 1 μM), reduced cancer cell proliferation (by 10-20%) and VEGF production (by 37%), aggressiveness and metastatic potential of primary tumors through inducing mesenchymal-to-epithelial transition, increased antitumor immune response, OXPHOS and the TCA cycle. Part of these effects was due to activation of TGR5 by LCA. Early stage breast cancer patients, versus control women, had reduced serum LCA levels, reduced chenodeoxycholic acid to LCA ratio, and reduced abundance of the baiH (7α/β-hydroxysteroid dehydroxylase, the key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial generation of LCA in early breast cancer. |
| Databáze: | OpenAIRE |
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