Ursodeoxycholic Acid Can Suppress Deoxycholic Acid-Induced Apoptosis by Stimulating Akt/PKB-Dependent Survival Signaling

The nontoxic bile acid ursodeoxycholic acid (UDCA) is reported to be an anti-apoptotic agent with efficacy against a variety of death stimuli including the cytotoxic bile acid deoxycholic acid (DCA). To gain insight into this anti-apoptotic property, we tested UDCA for its ability to protect the colon carcinoma-derived cell line HCT116 against DCA-induced apoptosis. We found that UDCA could suppress DCA-induced apoptosis in a time- and dose-dependent manner and that this effect correlated with Akt phosphorylation. Importantly, UDCA lost its ability to protect cells from DCA-induced cell death when Akt activity was suppressed genetically using a dominant negative Akt mutant or when PI3K activity was inhibited pharmacologically. These results suggest that UDCA can protect HCT116 cells against DCA-induced apoptosis by stimulating Akt-dependent survival signaling.