Differential sensitivities of recombinant human topoisomerase IIα and β to various classes of topoisomerase II interacting agents

被引：25

作者：

Perrin, D ^{[1
]}

van Hille, B ^{[1
]}

Hill, BT ^{[1
]}

机构：

[1] Ctr Rech Pierre Fabre, Dept Expt Cancerol 1, Div Expt Cancerol 1, F-81106 Castres, France

来源：

BIOCHEMICAL PHARMACOLOGY | 1998年 / 56卷 / 04期

关键词：

topoisomerase II alpha; topoisomerase II beta; catalytic activity; antitumour agents; DNA-decatenation; topoisomerase II-interacting agents;

D O I：

10.1016/S0006-2952(98)00082-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A series of topoisomerase-interacting antitumour agents were tested for their ability to differentially inhibit the catalytic activity of either topoisomerase (TOPO) II alpha 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 rumours preferentially expressing either the oc or the beta isoform may be differentially responsive to various classes of TOPO II-interacting agents. BIOCHEM PHARMACOL 56;4:503-507, 1998. (C) 1998 Elsevier Science Inc.

引用

页码：503 / 507

页数：5

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