Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation.
BACKGROUND
Deoxycholic acid has long been attributed as a tumour promoter in the colon. It exerts its growth-related actions in a phorbol ester-like manner, by stimulating protein kinase C. The aim of this study was to investigate the effect of deoxycholic acid on proliferation and apoptosis in the colon, by exposing colon cancer cells to it in increasing concentrations.


METHODS
Human colon cancer cells (Caco-2 and HT-29) were treated with deoxycholate or its two structural isomers, 3-beta-12-alpha-dihydroxy-5-beta-cholan-24-oic acid and 3-alpha-12-beta-dihydroxy-5-beta-cholan-24-oic acid. Proliferation was evaluated by cell counting, and apoptosis by estimating percentage cell survival and assessment of nuclear morphology.


RESULTS
Within the concentration range of up to 20 microM, deoxycholate stimulated growth of both human colon cancer cell lines. Its growth-promoting effect was abolished after inhibition of protein kinase C. At concentrations above 100 microM, deoxycholate induced apoptosis in both cell lines. Epimers of deoxycholate were significantly less potent in stimulating growth.


CONCLUSIONS
Low-dose deoxycholate stimulates colon cancer cell proliferation while > 100 micromol L(-1) of this secondary bile acid induces apoptosis in colon cancer cells. Deoxycholate might promote the likelihood of malignant transformation by increasing epithelial cell turnover in the colon.
Milovic
V
V
Johann Wolfgang Goethe University, Frankfurt, Germany. Milovic@em.uni-frankfurt.de
Teller
I C
IC
Faust
D
D
Caspary
W F
WF
Stein
J
J
D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000494:pharmacology; D018938:Caco-2 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D003840:Deoxycholic Acid / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology*; D019073:HT29 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism
D001647:Bile Acids and Salts; D003902:Detergents; D003840:Deoxycholic Acid; D011493:Protein Kinase C