Abstract
The protein kinase C inhibitor, staurosporine derivative CGP 41 251, was more efficient than staurosporine in the reversal of decreased anthracycline uptake in the anthracycline-resistant cell subline (A2780/ADR) of ovarian carcinoma. Staurosporine was more efficient than CGP 41 251 in the induction of cytometrically determined DNA fragmentation (cytofluorometric equivalent of apoptosis) in A2780 parental human ovarian carcinoma cells compared with the drug-resistant A2780/ADR subline and in both human leukemia K-562 cells as well as mouse leukemia L1210 compared with the araC-resistant L1210 cells. Staurosporine was a more potent inhibitor than CGP 41 251 of DNA synthesis in both araC-sensitive and -resistant mouse leukemia L1210 cells. CGP 41 251 was a slightly more efficient inhibitor of thymidine incorporation than staurosporine in human leukemia K-562 cells and its combination with araC had a higher inhibitory effect on the DNA synthesis in this cell line than staurosporine. CGP 41 251 exerted DNA synthesis inhibitory effects on both araC-sensitive and -resistant L1210 cells. Staurosporine-induced DNA synthesis inhibition in both araC-resistant and -sensitive L1210 mouse leukemia cells was decreased after combined administration with araC.
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