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Modulation of human Caco-2 intestinal epithelial cell phenotype by protein kinase C inhibitors

✍ Scribed by Marc D. Basson; Fu Hong

Publisher
Elsevier Science
Year
1995
Tongue
English
Weight
435 KB
Volume
19
Category
Article
ISSN
1065-6995

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✦ Synopsis

Abstract

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.

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