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Bioinorganic Chemistry and Applications
Volume 2012, Article ID 756374, 9 pages
http://dx.doi.org/10.1155/2012/756374
Research Article

DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7

1Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yu-Shan Road, Qingdao 266003, China
2The Department of Pharmacy, Qingdao Women and Children Hospital, 127 Liao-Yang West Road, Qingdao 266034, China

Received 17 July 2012; Revised 17 August 2012; Accepted 17 August 2012

Academic Editor: Zhe-Sheng Chen

Copyright © 2012 Xiao-mei Mo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal anticancer agents in combination to its low toxicity. Here, we found a vanadium compound Van-7 as an inhibitor of Topo I other than Topo II using topoisomerase-mediated supercoiled DNA relaxation assay. Agarose gel electrophoresis and comet assay showed that Van-7 treatment did not produce cleavable complexes like HCPT, thereby suggesting that Topo I inhibition occurred upstream of the relegation step. Further studies revealed that Van-7 inhibited Topo I DNA binding involved in its intercalating DNA. Van-7 did not affect the catalytic activity of DNase I even up to100 μM. Van-7 significantly suppressed the growth of cancer cell lines with IC50 at nanomolar concentrations 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.