Effect of daunorubicin, carminomycin, idarubicin and 4-demethoxydaunorubicinol against human normal myeloid stem cells and human malignant cells in vitro.
The cytotoxic effect of daunorubicin, carminomycin, idarubicin and the major metabolite of idarubicin in man, 4-demethoxydaunorubicinol, was investigated in a human normal progenitor myeloid stem cell assay and in a human tumor stem cell assay. Against normal myeloid progenitor cells, idarubicin and carminomycin were equally potent; both agents were significantly (P less than or equal to 0.01) more potent than daunorubicin. Idarubicin was approx. 2.5 times more potent than 4-demethoxydaunorubicinol. Against malignant tumor cells, 50% cell kill after exposure to idarubicin was observed in four out 24 samples; this inhibition occurred at a drug concentration of 0.1 micrograms/ml. Two of the samples sensitive to idarubicin were also sensitive to 4-demethoxydaunorubicinol at a concentration of 0.1 micrograms/ml. Overall, idarubicin was active against two out of six ovarian carcinomas and against one out of three breast carcinomas. Our data confirm that 4-demethoxydaunorubicinol may play a role in the biological activity of idarubicin.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D002360:Carubicin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015255:Idarubicin; D066298:In Vitro Techniques; D013234:Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D002360:Carubicin; D015255:Idarubicin; D003630:Daunorubicin