Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation

• Published in: European journal of clinical investigation Vol. 32; no. 1; pp. 29 - 34
• Main Authors: Milovic, V., Teller, I. C., Faust, D., Caspary, W. F., Stein, J.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-01-2002; Blackwell; Blackwell Publishing Ltd
• Subjects: Apoptosis - drug effects; Bile Acids and Salts - pharmacology; Bile salts; Biological and medical sciences; Caco-2 Cells - cytology; Caco-2 Cells - drug effects; Caco-2 Cells - enzymology; cell culture; Cell Division - drug effects; colon cancer; Colonic Neoplasms - pathology; Deoxycholic Acid - pharmacology; Detergents - pharmacology; epithelial cell proliferation; Gastroenterology. Liver. Pancreas. Abdomen; HT29 Cells - cytology; HT29 Cells - drug effects; HT29 Cells - enzymology; Humans; Intestinal Mucosa - pathology; Medical sciences; protein kinase C; Protein Kinase C - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Cell proliferation; Protein kinase C; Enzyme; Transferases; Low dose; Malignant tumor; Colonic disease; Acids; Cell death; Malignant transformation; Established cell line; Turnover; Digestive diseases; Intestinal disease; Epithelial cell; Colon; Apoptosis
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.0014-2972.2001.00938.x

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 µM, 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 µM, deoxycholate induced apoptosis in both cell lines. Epimers of deoxycholate were significantly less potent in stimulating growth.
Conclusion  Low‐dose deoxycholate stimulates colon cancer cell proliferation while > 100 µmol 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.