The role of bile acids in carcinogenesis

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

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.

• Jezik: Angleški jezik
• Ključne besede: 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
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 39 str.
• Številčenje: Vol. 79, iss. 5, art. 243
• PID: 20.500.12556/RUL-165903
• UDK: 616.3
• ISSN pri članku: 1420-9071
• DOI: 10.1007/s00018-022-04278-2
• COBISS.SI-ID: 105338883
• Datum objave v RUL: 13.12.2024

Gradivo je del revije

• Naslov: Cellular and molecular life sciences
• Skrajšan naslov: Cell. mol. life sci.
• Založnik: Springer Nature
• ISSN: 1420-9071
• COBISS.SI-ID: 512007961

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: žolčna kislina, muskarinski receptor, želodčni rak