Altered drug sensitivity in response to idarubicin treatment in K562 human leukaemia cells.
Relative to the commonly used anthracyclines, little is known about idarubicin and the development of multidrug resistance. We have previously shown the K562/IDA subline resulting from intermittent treatment of the K562 human leukaemia cell line with 20 ng/ml idarubicin did not develop multidrug resistance but became more sensitive to etoposide. Additional similar treatments of this subline produced the K562/IDA20 subline which partially retained its etoposide sensitivity although these cells expressed P-glycoprotein and were resistant to paclitaxel. Sensitization to etoposide was associated with increased decatenation activity of topoisomerase II, although there were no changes in topoisomerase IIalpha expression or formation of etoposide-dependent cleavable complexes. In comparison, the K562/IDA10 subline produced by intermittent treatment of the K562 cells, firstly with 5 ng/ml then 10 ng/ml idarubicin, showed no detectable expression of P-glycoprotein, decreased topoisomerase IIalpha expression and increased resistance to etoposide and amsacrine, but not to idarubicin or genistein. Even though intermittent treatment with idarubicin caused increased drug resistance in both sublines, they remained sensitive to idarubicin. Therefore the potential of idarubicin as a substitute for other anthracyclines in the treatment of cancer warrants further investigation.
Locke
V L
VL
Department of Cell and Molecular Biology, University of Technology, Sydney, Gore Hill, NSW, Australia.
Davey
R A
RA
Davey
M W
MW
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D018432:Drug Resistance, Multiple; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II; D015255:Idarubicin