Ursodeoxycholic acid inhibits translocation of protein kinase C in human colonic cancer cell lines

• Published in: European journal of cancer (1990) 2005-09, Vol.41 (14), p.2160-2169
• Main Authors: Shah, Syed A., Looby, Eileen, Volkov, Yuri, Long, Aideen, Kelleher, Dermot
• Format: Article
• Language: English
• Subjects: Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cell Shape; Colonic Neoplasms - enzymology; Colonic Neoplasms - prevention & control; Colorectal cancer; Deoxycholic acid; Deoxycholic Acid - pharmacology; Green Fluorescent Proteins - metabolism; Humans; Medical sciences; Pharmacology. Drug treatments; Protein Kinase C; Protein Kinase C - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transfection - methods; Tumors; Ursodeoxycholic acid; Ursodeoxycholic Acid - pharmacology
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2005.06.015

Deoxycholic acid (DCA) has been implicated in colonic carcinogenesis through effects mediated by protein kinase C (PKC) activation. By contrast, ursodeoxycholic acid (UDCA) is reported to reduce colon cancer incidence in ulcerative colitis. The aim of this study was to investigate whether UDCA modulated DCA-induced PKC isoenzyme translocation to its site of activity. HCT116 cells were treated with DCA, UDCA alone or pre-treated with UDCA followed by DCA. Analysis of translocation of endogenous and enhanced green fluorescent protein (EGFP) constructs of PKC isoenzymes was performed. Both DCA and phorbol myristate acetate (PMA) but not UDCA caused translocation of endogenous PKC α, ε and δ and transfected PKC β1-, ε- and δ-EGFP from cytosol to plasma membrane, reflecting isoenzyme activation. Furthermore, UDCA inhibited DCA-induced translocation of PKC isoenzymes. Inhibition of DCA-induced PKC translocation may be a mechanism for UDCA-mediated chemoprevention of colon carcinogenesis.