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Altered drug sensitivity in response to idarubicin treatment in K562 human leukaemia cells
Author(s) -
Locke Vicki L.,
Davey Ross A.,
Davey Mary W.
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01494.x
Subject(s) - idarubicin , etoposide , amsacrine , topoisomerase , pharmacology , biology , k562 cells , multiple drug resistance , p glycoprotein , drug resistance , doxorubicin , rhodamine 123 , chemotherapy , medicine , cancer research , immunology , cytarabine , biochemistry , enzyme , leukemia , genetics
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 IIα 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 IIα 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.