Different functional states of topoisomerase II can be discriminated by orthovanadate sensitivity in multi-drug resistant human leukemic cells.
We have studied the functional properties of topoisomerase II (Topo II) in a subclone of the HL-60 cell line, which is highly resistant to cytotoxic Topo II inhibitors, but does not express p-glycoprotein. The cells contain the two forms of human topo II with Mr 170 and 180 kDa in equal proportions. Two different states of both forms of the enzymes can be separated by anion-exchange chromatography and functionally discriminated on the basis of orthovanadate sensitivity. The EC50 of orthovanadate was 0.2 microM for the early eluting and 30 microM for the late eluting Topo II.
Department of Internal Medicine, University Hospital, Würzburg, Federal Republic of Germany.
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Boege
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Gieseler
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Biersack
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Meyer
D000255:Adenosine Triphosphate / Q000378:metabolism; D000495:Allosteric Site; D000677:Amsacrine / Q000494:pharmacology*; D002852:Chromatography, Ion Exchange; D002999:Clone Cells / Q000187:drug effects / Q000201:enzymology; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000473:pathology*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D017354:Point Mutation; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology*
D007527:Isoenzymes; D009363:Neoplasm Proteins; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D014638:Vanadates; D005047:Etoposide; D000255:Adenosine Triphosphate; D004250:DNA Topoisomerases, Type II