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DNA binding and topoisomerase inhibitory activity of a novel vanadium compound van-7

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Document pages: 9 pages

Abstract: In recent years, vanadium compounds are considered as the representative of a new class of non platinum metal anticancer agents because of their low toxicity. Here, we use topoisomerase mediated supercoiled DNA relaxation analysis to find that vanadium compound van-7 is an inhibitor of topoisomerase I rather than topoisomerase II. Agarose gel electrophoresis and comet assay showed that Van-7 treatment did not produce cleavage complexes like HCPT, thus indicating that topoisomerase I inhibition occurred upstream of the downgrading step. Further studies showed that van-7 inhibited the binding of topoisomerase I to its inserted DNA. Van-7 had no effect on the catalytic activity of DNase-I, even up to 100   μ M. Van-7 significantly inhibited the growth of IC50 cancer cell line at nanomolar concentrationons and arrested cell cycle of A549 cells at G2 M phase. All these results indicate that Van-7 is a potential selective Topo I inhibitor with anticancer activities as a kind of Topo I suppressor, not Topo I poison.

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