Role of protein kinase C in adriamycin-induced erythroid differentiation of K562 cells.
Modulators of protein kinase C (PKC) were used to investigate the role of this enzyme during Adriamycin-induced erythroid differentiation of K562 cells. Adriamycin (0.1 microM) induced erythroid differentiation in 60% +/- 10% of K562 cells. Phorbol myristate-12-acetate, an activator of protein kinase C, was strongly anti-proliferative to K562 cells (IC50, 8 nM) but did not induce erythroid differentiation. Staurosporine inhibited PKC from K562 cells (IC50, 8 nM) and blocked Adriamycin-induced erythroid differentiation, but only at concentrations marginally below those that inhibited proliferation (IC50, 81 nM), 1-(5-Isoquinolinylsulphonyl)-2-methylpiperazine (H-7) inhibited K562 PKC (IC50, 26 microM) but reduced Adriamycin-induced differentiation by less than 50% at concentrations of up to 600 microM. These data argue against a major role for PKC during Adriamycin-induced erythroid differentiation in K562 cells.
Hoffman
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CRC Laboratories, Charing Cross Hospital, London, UK.
Newlands
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D046508:Culture Techniques; D004317:Doxorubicin / Q000494:pharmacology*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D004317:Doxorubicin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate