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Abstract
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.
Keywords
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)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
March 16,
1992
Received:
January 19,
1992
Identification
Copyright
© 1992 Published by Elsevier Inc.