MODULATION OF HUMAN CACO-2 INTESTINAL EPITHELIAL-CELL PHENOTYPE BY PROTEIN-KINASE-C INHIBITORS

Protein kinase C (PKC) isoforms are altered in colon tumors and upon e xposure of intestinal mucosa to nutrients. We evaluated the effects of the PKC inhibitors staurosporine and calphostin C on human Caco-2 int estinal epithelial proliferation, motility and differenfiation. Motili ty was quantified by monolayer expansion and the brush border enzymes dipeptidyl dipeptidase (DPDD) and alkaline phosphatase (AP) by synthet ic substrate digestion. Staurosporine (0.03-1.0 ng/ml) and calphostin C (10(-12)M-10(-4) M) dose-dependently inhibited monolayer expansion a nd AP but stimulated DPDD. Proliferation was also inhibited but the ef fects of each inhibitor on motility, AP, and DPDD were preserved after mitomycin C proliferative blockade, suggesting that these effects wer e proliferation-indepentent. PKC inhibitors independently inhibit moti lity, AP and proliferation in human intestinal Caco-2 epithelial cells , but selectively stimulate the small intestinal differentiation marke r DPDD. PKC may regulate small intestinal epithelial differentiation.