Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness.
Biochim Biophys Acta Bioenerg
; 1859(9): 958-974, 2018 09.
Article
in En
| MEDLINE
| ID: mdl-29655782
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/ß-hydroxysteroid dehydroxylase, the key enzyme in LCA generation) gene in fecal DNA, all suggesting reduced microbial generation of LCA in early breast cancer.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Bacteria
/
Breast Neoplasms
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Cell Movement
/
Apoptosis
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Cell Proliferation
/
Detergents
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Lithocholic Acid
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
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Middle aged
Language:
En
Year:
2018
Type:
Article