Ursodeoxycholic acid inhibits translocation of protein kinase C in human colonic cancer cell lines.
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 alpha, epsilon and delta and transfected PKC beta1-, epsilon- and delta-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.
Shah
Syed A
SA
Department of Clinical Medicine and Dublin Molecular Medicine Centre, Trinity College and St. James's Hospital, Dublin, Ireland.
Looby
Eileen
E
Volkov
Yuri
Y
Long
Aideen
A
Kelleher
Dermot
D
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D048430:Cell Shape; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D003840:Deoxycholic Acid / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; C485184:enhanced green fluorescent protein; D003840:Deoxycholic Acid; D049452:Green Fluorescent Proteins; D014580:Ursodeoxycholic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate