The role of bile acids in carcinogenesis

Režen, Tadeja (author), Rozman, Damjana (author), Mikó, Edit (author)

Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The bulk of bile acid synthesis takes place in the liver yielding primary bile acids; however, other tissues have also the capacity to generate bile acids (e.g. ovaries). Hepatic bile acids are then transported to bile and are subsequently released into the intestines. In the large intestine, a fraction of primary bile acids is converted to secondary bile acids by gut bacteria. The majority of the intestinal bile acids undergo reuptake and return to the liver. A small fraction of secondary and primary bile acids remains in the circulation and exert receptor-mediated and pure chemical effects (e.g. acidic bile in oesophageal cancer) on cancer cells. In this review, we assess how changes to bile acid biosyn- thesis, bile acid flux and local bile acid concentration modulate the behavior of different cancers. Here, we present in-depth the involvement of bile acids in oesophageal, gastric, hepatocellular, pancreatic, colorectal, breast, prostate, ovarian cancer. Previous studies often used bile acids in supraphysiological concentration, sometimes in concentrations 1000 times higher than the highest reported tissue or serum concentrations likely eliciting unspecific effects, a practice that we advocate against in this review. Furthermore, we show that, although bile acids were classically considered as pro-carcinogenic agents (e.g. oesophageal cancer), the dogma that switch, as lower concentrations of bile acids that correspond to their serum or tissue reference concentration possess anticancer activity in a subset of cancers. Differences in the response of cancers to bile acids lie in the differential expression of bile acid receptors between cancers (e.g. FXR vs. TGR5). UDCA, a bile acid that is sold as a generic medication against cholestasis or biliary surge, and its conjugates were identified with almost purely anticancer features suggesting a possibility for drug repurposing. Taken together, bile acids were considered as tumor inducers or tumor promoter molecules; nevertheless, in certain cancers, like breast cancer, bile acids in their reference concentrations may act as tumor suppressors suggesting a Janus-faced nature of bile acids in carcinogenesis.

• Language: English
• Keywords: bile acid, muscarinic receptor, gastric cancer, primary bile acid, secondary bile acid, bile acid biosynthesis, bile acid receptors, bile acid transporters, microbiome, CA, CDCA, DCA, LCA, UDCA, carcinogenesis, TGR5, S1PR2, muscarinic receptor CHRM2, muscarinic receptor CHRM3, FXR, PXR, CAR, VDR, LXR, SHP, oesophageal carcinoma, hepatocellular carcinoma, pancreatic adenocarcinoma, colorectal carcinoma, breast cancer, prostate cancer, ovarian cancer, epithelial–mesenchymal transition, oxidative stress, Warburg metabolism
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 39 str.
• Numbering: Vol. 79, iss. 5, art. 243
• PID: 20.500.12556/RUL-165903
• UDC: 616.3
• ISSN on article: 1420-9071
• DOI: 10.1007/s00018-022-04278-2
• COBISS.SI-ID: 105338883
• Publication date in RUL: 13.12.2024

Record is a part of a journal

• Title: Cellular and molecular life sciences
• Shortened title: Cell. mol. life sci.
• Publisher: Springer Nature
• ISSN: 1420-9071
• COBISS.SI-ID: 512007961

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: žolčna kislina, muskarinski receptor, želodčni rak