DIFFERENTIAL SENSITIVITIES OF RECOMBINANT HUMAN TOPOISOMERASE-II-ALPHA AND TOPOISOMERASE-II-BETA TO VARIOUS CLASSES OF TOPOISOMERASE-II INTERACTING AGENTS
D. Perrin et al., DIFFERENTIAL SENSITIVITIES OF RECOMBINANT HUMAN TOPOISOMERASE-II-ALPHA AND TOPOISOMERASE-II-BETA TO VARIOUS CLASSES OF TOPOISOMERASE-II INTERACTING AGENTS, Biochemical pharmacology, 56(4), 1998, pp. 503-507
A series of topoisomerase-interacting antitumour agents were tested fo
r their ability to differentially inhibit the catalytic activity of ei
ther topoisomerase (TOPO) II alpha or beta, as judged by a DNA decaten
ation assay. The alpha form, relative to the beta isoform, proved 1 to
3 times more sensitive to nonintercalating complex-stabilizing TOPO I
I-interacting agents (etoposide and derivatives) and up to 18 times mo
re 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 exp
ressing either the oc or the beta isoform may be differentially respon
sive to various classes of TOPO II-interacting agents. BIOCHEM PHARMAC
OL 56;4:503-507, 1998. (C) 1998 Elsevier Science Inc.