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Bioinorg Chem Appl. 2012; 2012: 756374.
Published online Sep 30, 2012. doi:  10.1155/2012/756374
PMCID: PMC3465879
DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7
Xiao-mei Mo, 1 , 2 Zhan-fang Chen, 2 Xin Qi, 1 Yan-tuan Li, 1 and Jing Li 1 *
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
*Jing Li: lijing_ouc/at/
Academic Editor: Zhe-Sheng Chen
Received July 17, 2012; Revised August 17, 2012; Accepted August 17, 2012.
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.
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