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Pharmacology & Therapeutics

Pharmacology & Therapeutics

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Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy

Published:1 November 2019 DOI: 10.1016/j.pharmthera.2019.107396 PMID: 31356908
Jean-Fran?ois Goossens , Christian Bailly

Abstract

Ursodeoxycholic acid (UDCA) is a secondary bile acid issued from the transformation of (cheno)deoxycholic acid by intestinal bacteria, acting as a key regulator of the intestinal barrier integrity and essential for lipid metabolism. UDCA is also a long-established drug, largely used for the dissolution of cholesterol gallstones, the treatment of primary biliary cholangitis and other hepatobiliary disorders. The history of UDCA is briefly retraced here as well as its multifactorial mechanism of action, based on its anti-inflammatory, antioxidant and cytoprotective activities. The present review is centred around the anticancer properties of UDCA and synthetic antitumor derivatives designed over the past 20?years. Paradoxically, depending on the conditions, UDCA exhibits both pro- and anti-apoptotic properties toward different cell types. In particular, the UDCA drug can protect epithelial cells from damages and apoptosis while inducing inhibition of proliferation and apoptotic and/or autophagic death of cancer cells. The effects of UDCA on cancer cell migration, cancer stem cells and drug-induced dysbiosis are also evoked. The drug has revealed modest activities against colon and gastric cancers but may be useful to improve treatments of hepatocellular carcinoma, notably in combination with other drugs such as sorafenib. UDCA can also protect from damages induced by cancer chemotherapeutic agents. The potential of UDCA in cancer, as a chemo-protecting or chemotherapeutic agent, is highlighted here as well as the design of tumour-active derivatives, including UDCA-drug conjugates. A repurposing of UDCA in oncology should be further considered.

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Ursodeoxycholic acid 128-13-2 C24H40O4 907 suppliers $10.00-$3418.80
Sorafenib 284461-73-0 C21H16ClF3N4O3 658 suppliers $8.00-$756.25

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