Anti-cancer copper salicylaldoxime complex inhibits topoisomerase II catalytic activity

Topoisomerase II (topo II) is a potential cellular target for a number of a nti-cancer drugs. To elucidate the possible mechanism for anti-proliferatio n activity of copper salicylaldoxime (CuSAL), which was earlier shown to ef fectively inhibit the L1210 leukaemia cell proliferation, effect of the dru g on topo II relaxation activity was studied. The results show that the rel axation activity of topo Il was completely inhibited at 300 muM CuSAL conce ntration. To characterize the mode of inhibition by CuSAL, drug-induced top o 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 Il dimerization, whi ch may lead to the formation of single-strand breaks.