PKC412 induces apoptosis through a caspase-dependent mechanism in human keloid-derived fibroblasts

Ayako Nakazono-Kusaba, Fumi Takahashi-Yanaga, Yoshikazu Miwa, Sachio Morimoto, Masutaka Furue, Toshiyuki Sasaguri

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

There is no established pharmacological therapy for skin keloids, a wound healing disorder. In this study, we investigated the effect of N-benzoyl staurosporine (PKC412), a protein kinase C inhibitor, on human keloid-derived fibroblasts to examine whether this agent is applicable for the treatment of keloid formation. Although PKC412 induced apoptosis in keloid fibroblasts in a time- and dose-dependent manner, the effective concentration of this agent was much higher than that of staurosporine. Western blotting showed that both PKC412 (10 μM) and staurosporine (100 nM) cleaved pro-caspase-3 to active forms. An in vitro caspase assay also showed that PKC412 and staurosporine elevated caspase-3 activities. Carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK), a caspase inhibitor with a broad spectrum, inhibited caspase-3 activities stimulated by PKC412 and staurosporine; however, only PKC412-induced apoptosis, but not staurosporine-induced apoptosis, was prevented by Z-VAD-FMK. These results suggested that PKC412-induced apoptosis, but not staurosporine-induced apoptosis, is mainly mediated by the caspase-dependent mechanism.

Original languageEnglish
Pages (from-to)155-160
Number of pages6
JournalEuropean Journal of Pharmacology
Volume497
Issue number2
DOIs
Publication statusPublished - Aug 23 2004

All Science Journal Classification (ASJC) codes

  • Pharmacology

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