Development of drug resistance is reduced with idarubicin relative to other anthracyclines.
Multidrug resistance (MDR) is associated with poor prognosis in leukemia, and anthracyclines, which are used in the treatment of leukemia, are associated with the expression of P-glycoprotein and the development of MDR. We report here that idarubicin, a new anthracycline approved for use in the treatment of acute myelogenous leukemia (AML), did not induce P-glycoprotein expression in the K562 human leukemia cell line under conditions where daunorubicin, doxorubicin and epirubicin did induce expression of P-glycoprotein. The P-glycoprotein expressing, multidrug resistant sublines developed to daunorubicin (K/DNR), doxorubicin (K/DOX) and epirubicin (K/EPR) were cross-resistant to the other anthracyclines and to vinblastine, taxol, colchicine and actinomycin D, but were not resistant to idarubicin or etoposide. The idarubicin treated subline, K/IDA, was only resistant to taxol but was 12-fold sensitized to etoposide, suggesting that idarubicin had affected topoisomerase II in this subline.
Hargrave
R M
RM
Neurobiology Unit, University of Technology, Sydney, NSW, Australia.
Davey
M W
MW
Davey
R A
RA
Kidman
A D
AD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D005047:Etoposide; D014700:Verapamil; D015255:Idarubicin