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 exposure of intestinal mucosa to nutrients. We evaluated the effects of the PKC inhibitors staurosporine and calphostin C on human Caco-2 intestinal epithelial proliferation, motility, and differentiation. Motility was quantitated by monolayer expansion and the brush border enzymes dipeptidyl dipeptidase (DPDD) and alkaline phosphatase (AP) by synthetic substrate digestion. Staurosporine (0.03-1.0 ng/ml) and calphostin C (10(-12) M-10(-4) M) dose-dependently inhibited monolayer expansion and AP but stimulated DPDD. Proliferation was also inhibited but the effects of each inhibitor on motility, AP, and DPDD were preserved after mitomycin C proliferative blockade, suggesting that these effects were proliferation-independent. PKC inhibitors independently inhibit motility, AP and proliferation in human intestinal Caco-2 epithelial cells, but selectively stimulate the small intestinal differentiation marker DPDD. PKC may regulate small intestinal epithelial differentiation.
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
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D018938:Caco-2 Cells / Q000187:drug effects / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008871:Microvilli / Q000201:enzymology; D016685:Mitomycin / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010641:Phenotype; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D019384:Nucleic Acid Synthesis Inhibitors; D016685:Mitomycin; D003094:Collagen; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C