Deoxycholic Acid Can Induce Apoptosis in the Human Colon Cancer Cell Line HCT116 in the Absence of Bax

Abstract

In the human colon cancer cells HCT116, deoxycholic acid (DCA) induces apoptosis via the mitochondrial pathway by triggering the release of mitochondrial factors such as cytochrome c. To elucidate if Bax, a proapoptotic member of the Bcl-2 family known to trigger cytochrome c release in response to various types of apoptotic stimuli, is involved in DCA-induced apoptosis in HCT116 cells, we analyzed DCA-induced apoptosis in Bax-knockout (Bax^–/–) HCT116 cells. Cytochrome c release and caspase-9 activation were detectable after 5 min in both Bax^–/– and Bax^+/– HCT116 cells. Caspase-3 and caspase-8 activation was observed after 15 and 30 min, respectively. Bax^–/– cells were protected from apoptosis by treating them with ursodeoxycholic acid for 12 h prior to DCA treatment. These results are consistent with our previous observations that were obtained by using wild-type HCT116 cells and suggest that Bax is not indispensable for DCA-induced apoptosis in HCT116 cells.

ACKNOWLEDGMENTS

The authors thank Dr. Vogelstein (Johns Hopkins Medical School) for the gift of HCT116 Bax^+/– and Bax^–/– cells and Drs. Kazumitsu Ueda and Noriyuki Kioka (Kyoto University) for providing microscope equipment.