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.
Im
Eunok
E
Arizona Cancer Center, Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724, USA.
Akare
Sandeep
S
Powell
Ashley
A
Martinez
Jesse D
JD
D017209:Apoptosis / Q000187:drug effects*; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014580:Ursodeoxycholic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D011518:Proto-Oncogene Proteins; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt