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 comp osition of fecal bile acids are important determining factors in the e tiology of colon cancer. However, the mechanism by which these compoun ds influence tumor development is not understood. To begin to elucidat e their mechanism of action, four bile acids, cholic acid, chenodeoxyc holic acid, deoxycholic acid (DCA), and ursodeoxycholic acid, were exa mined for their effects on the growth of several different tumor cell lines. We found that incubating cells with chenodeoxycholic acid or DC A 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 nor induce a poptosis. Cholic acid had no discernible effect on cells. Notably, the apoptosis induced by DCA could be suppressed by inhibiting protein ki nase C activity with calphostin C. These results indicate that differe nt bile acids exhibit distinct biological activities and suggest that the cytotoxicity reported for DCA may be due to ifs capacity to induce apoptosis via a protein kinase C-dependent signaling pathway.