title: Development of drug resistance is reduced with idarubicin relative to other anthracyclines.
abstract: 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.
authors.affiliation: Neurobiology Unit, University of Technology, Sydney, NSW, Australia.
authors.forename: R M
authors.initials: RM
authors.lastname: Hargrave
authors.forename: M W
authors.initials: MW
authors.lastname: Davey
authors.forename: R A
authors.initials: RA
authors.lastname: Davey
authors.forename: A D
authors.initials: AD
authors.lastname: Kidman
mesh_terms: 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
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D005047:Etoposide; D014700:Verapamil; D015255:Idarubicin