Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation.
Epidemiological studies have suggested that the concentration and composition of fecal bile acids are important determining factors in the etiology of colon cancer. However, the mechanism by which these compounds influence tumor development is not understood. To begin to elucidate their mechanism of action, four bile acids, cholic acid, chenodeoxycholic acid, deoxycholic acid (DCA), and ursodeoxycholic acid, were examined for their effects on the growth of several different tumor cell lines. We found that incubating cells with chenodeoxycholic acid or DCA caused morphological changes, seen by electron and light microscopy, that were characteristic of apoptosis, whereas incubating cells with ursodeoxycholic acid inhibited cell proliferation but did not induce apoptosis. Cholic acid had no discernible effect on cells. Notably, the apoptosis induced by DCA could be suppressed by inhibiting protein kinase C activity with calphostin C. These results indicate that different bile acids exhibit distinct biological activities and suggest that the cytotoxicity reported for DCA may be due to its capacity to induce apoptosis via a protein kinase C-dependent signaling pathway.
Department of Radiation Oncology, Arizona Cancer Center, Tucson 85724, USA. JMARTINEZ@AZCC.ARIZONA.EDU
J D
JD
Martinez
E D
ED
Stratagoules
J M
JM
LaRue
A A
AA
Powell
P R
PR
Gause
M T
MT
Craven
C M
CM
Payne
M B
MB
Powell
E W
EW
Gerner
D L
DL
Earnest
D016588:Anticarcinogenic Agents / Q000378:metabolism*; D017209:Apoptosis; D001647:Bile Acids and Salts / Q000378:metabolism*; D002273:Carcinogens / Q000009:adverse effects*; D002455:Cell Division; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D019826:Cholic Acid / Q000378:metabolism; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000009:adverse effects*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D001647:Bile Acids and Salts; D002273:Carcinogens; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D019826:Cholic Acid