DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7
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 superc...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Bioinorganic Chemistry and Applications |
| Online Access: | http://dx.doi.org/10.1155/2012/756374 |
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| author | Xiao-mei Mo Zhan-fang Chen Xin Qi Yan-tuan Li Jing Li |
| author_facet | Xiao-mei Mo Zhan-fang Chen Xin Qi Yan-tuan Li Jing Li |
| author_sort | Xiao-mei Mo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bfad09c1e49b40f0b1d30d9b6a47e923 |
| institution | DOAJ |
| issn | 1565-3633 1687-479X |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioinorganic Chemistry and Applications |
| spelling | doaj-art-bfad09c1e49b40f0b1d30d9b6a47e9232025-08-20T03:22:39ZengWileyBioinorganic Chemistry and Applications1565-36331687-479X2012-01-01201210.1155/2012/756374756374DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7Xiao-mei Mo0Zhan-fang Chen1Xin Qi2Yan-tuan Li3Jing Li4Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yu-Shan Road, Qingdao 266003, ChinaThe Department of Pharmacy, Qingdao Women and Children Hospital, 127 Liao-Yang West Road, Qingdao 266034, ChinaKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yu-Shan Road, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yu-Shan Road, Qingdao 266003, ChinaKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yu-Shan Road, Qingdao 266003, ChinaVanadium 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.http://dx.doi.org/10.1155/2012/756374 |
| spellingShingle | Xiao-mei Mo Zhan-fang Chen Xin Qi Yan-tuan Li Jing Li DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 Bioinorganic Chemistry and Applications |
| title | DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 |
| title_full | DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 |
| title_fullStr | DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 |
| title_full_unstemmed | DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 |
| title_short | DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7 |
| title_sort | dna binding and topoisomerase i suppressing activities of novel vanadium compound van 7 |
| url | http://dx.doi.org/10.1155/2012/756374 |
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