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Various lines of evidence indicate that protein kinase C, a key enzyme in transmembraneous signal transduction, is involved in the regulation of keratinocyte proliferation. In the present study we have investigated the effects of various structurally unrelated protein kinase C inhibitors on the proliferation of HaCaT cells, a non-tumorigenic human keratinocyte cell line. All protein kinase C inhibitors dose-dependently inhibited cell proliferation as assessed by the incorporation of radioactively labelled thymidine and amino acids as well as the increase in total protein content in keratinocytes. The potencies of the drugs to inhibit cell proliferation were strongly correlated to their inhibitory potency on purified protein kinase C, displaying a correlation coefficient of 0.97. Methotrexate, an anti-proliferative drug, was found not to inhibit protein kinase C. Therefore, our data provide evidence that protein kinase C is crucially involved in the regulation of keratinocyte proliferation but is not the only target of anti-proliferative drug action.
Abbreviations:CaM (calmodulin), CP 46,665-1 (4-aminomethyl-1-[2,3-(di-n-decyloxy)n-proponyl]-4-phenylpiperidine dihydrochloride), DNA (deoxyribonucleic acid), PMA (phorbol-12-myristate-13-acetate), PKC (protein kinase C), PS (phosphatidyl-l-serine), W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide)
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Accepted: March 16, 1992
Received: January 19, 1992
© 1992 Published by Elsevier Inc.