Anti-cancer copper salicylaldoxime complex inhibits topoisomerase II catalytic activity

Abstract

Topoisomerase II (topo II) is a potential cellular target for a number of anti-cancer drugs. To elucidate the possible mechanism for anti-proliferation activity of copper salicylaldoxime (CuSAL), which was earlier shown to effectively inhibit the L1210 leukaemia cell proliferation, effect of the drug on topo II relaxation activity was studied. The results show that the relaxation activity of topo II was completely inhibited at 300 μM CuSAL concentration. To characterize the mode of inhibition by CuSAL, drug-induced topo II cleavage assay was conducted. The results show that CuSAL inhibits the enzyme activity through induction of enzyme-linked single-strand breaks in the DNA. Our data suggest that CuSAL may inhibit topo II dimerization, which may lead to the formation of single-strand breaks.