Deoxycholic acid-induced apoptosis is switched to necrosis by bcl-2 and calphostin C.
We previously demonstrated that the cytotoxicity associated with exposure of HCT116 cells to deoxycholic acid was due to the induction of apoptosis. Here we show that this results in activation of caspase 3 and that over expression of bcl-2 can suppress this. Surprisingly, inhibition of apoptosis by over expression of bcl-2 or incubation with calphostin C, a PKC inhibitor, did not enhance cell survival, but instead caused a switchover to death by necrosis. Hence, DCA-induced apoptosis requires caspase activity and both bcl-2 and PKC can determine the type of cell death induced by deoxycholic acid.
LaRue
J M
JM
Department of Radiation Oncology, The University of Arizona, 1501 N. Campbell Ave., P.O. Box 245024, Tucson 85724, USA.
Stratagoules
E D
ED
Martinez
J D
JD
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000494:pharmacology*; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology*; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009281:Naphthalenes; D019253:Proto-Oncogene Proteins c-bcl-2; C061465:calphostin complex; D003840:Deoxycholic Acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases