Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness.

Abstract

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.

• Authors: Edit Mikó, András Vida, Tünde Kovács, Gyula Ujlaki, György Trencsényi, Judit Márton, Zsanett Sári, Patrik Kovács, Anita Boratkó, Zoltán Hujber, Tamás Csonka, Péter Antal-Szalmás, Mitsuhiro Watanabe, Imre Gombos, Balazs Csoka, Borbála Kiss, László Vígh, Judit Szabó, Gábor Méhes, Anna Sebestyén, James J Goedert, Péter Bai
• Journal: Biochimica et biophysica acta. Bioenergetics (Biochim Biophys Acta Bioenerg) Vol. 1859 Issue 9 Pg. 958-974 (09 2018) ISSN: 0005-2728 [Print] Netherlands
• PMID: 29655782 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Detergents
• Lithocholic Acid

Topics

• Animals
• Apoptosis (drug effects)
• Bacteria (metabolism)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Detergents (pharmacology)
• Female
• Humans
• Lithocholic Acid (pharmacology)
• Mice
• Mice, Inbred BALB C
• Middle Aged
• Prognosis
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays