Altered drug sensitivity in response to idarubicin treatment in K562 humanleukaemia cells

Relative to the commonly used anthracyclines, little is known about idarubi cin and the development of multidrug resistance. We have previously shown t he K562/IDA subline resulting from intermittent treatment of the K562 human leukaemia cell line with 20 ng/ml idarubicin did not develop multidrug res istance but became more sensitive to etoposide. Additional similar treatmen ts of this subline produced the K562/IDA20 subline which partially retained its etoposide sensitivity although these cells expressed P-glycoprotein an d were resistant to paclitaxel, Sensitization to etoposide was associated w ith increased decatenation activity of topoisomerase II, although there wer e no changes in topoisomerase Lieu expression or formation of etoposide-dep endent cleavable complexes. In comparison, the K562/IDA10 subline produced by intermittent treatment of the K562 cells, firstly with 5 ng/ml then 10ng /ml idarubicin, showed no detectable expression of P-glycoprotein, decrease d topoisomerase II alpha expression and increased resistance to etoposide a nd 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 idarubi cin as a substitute for other anthracyclines in the treatment of cancer war rants further investigation.