Differential sensitivities of recombinant human topoisomerase IIalpha and beta to various classes of topoisomerase II-interacting agents.
A series of topoisomerase-interacting antitumour agents were tested for their ability to differentially inhibit the catalytic activity of either topoisomerase (TOPO) IIalpha or beta, as judged by a DNA decatenation assay. The alpha form, relative to the beta isoform, proved 1 to 3 times more sensitive to nonintercalating complex-stabilizing TOPO II-interacting agents (etoposide and derivatives) and up to 18 times more sensitive to non-complex-stabilizing inhibitors of TOPO II ((+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane [ICRF 159] and meso-2,3-bis(3,5-dioxopiperazine-1-yl)butane [ICRF 193]). However, the beta form of the enzyme appeared 1 to 3 times more sensitive to intercalating TOPO II-interacting agents (daunorubicin, aclarubicin and mitoxantrone). A possible implication of these data are that tumours preferentially expressing either the alpha or the beta isoform may be differentially responsive to various classes of TOPO II-interacting agents.
Division of Experimental Cancerology I, Centre de Recherche Pierre Fabre, Castres, France.
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Perrin
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van Hille
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Hill
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; D059005:Topoisomerase II Inhibitors