Emodin Triggers DNA Double-Strand Breaks by Stabilizing Topoisomerase II-DNA Cleavage Complexes and by Inhibiting ATP Hydrolysis of Topoisomerase II
文献类型：期刊论文
| 作者 | Li, Yan; Luan, Yang; Qi, Xinming ; Li, Ming; Gong, Likun; Xue, Xiang; Wu, Xiongfei; Wu, Yuanfeng; Chen, Min; Xing, Guozhen
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| 刊名 | TOXICOLOGICAL SCIENCES
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| 出版日期 | 2010-12 |
| 卷号 | 118期号:2页码:435-443 |
| ISSN号 | 1096-6080 |
| 关键词 | emodin DNA double-strand breaks topoisomerase II cleavage complexes ATP hydrolysis |
| DOI | 10.1093/toxsci/kfq282 |
| 文献子类 | Article |
| 英文摘要 | Emodin, an anthraquinone derived from a plant and fungi, has been reported to possess potential genotoxicity, but the mechanism is not entirely clear. Here, we report that emodin causes DNA double-strand breaks (DSBs) through stabilization of topoisomerase (Topo) II-DNA cleavage complexes and inhibition of ATP hydrolysis. In our study, emodin did not induce mutagenecity in the salmonella mutation assay but caused genotoxicity in the thymidine kinase gene mutation assay and in the micronucleus test. Moreover, emodin induced DNA DSBs demonstrated by induction of comet tails, the expression of phosphorylated histone H2AX, and phosphorylation of ataxia telangiectasia mutated. Our studies also revealed that emodin exerted strong inhibitory activity against Topo II in the supercoiled pBR322 relaxation assay and in Topo II-mediated kinetoplast DNA decatenation, similar to the previous report. We also showed that the inhibitory effect of emodin on Topo II was because of its ability to stabilize Topo II-DNA complexes and to inhibit the ATP hydrolysis of Topo II. Furthermore, emodin was found to trigger DNA DSBs in a Topo II-dependent manner using the Topo II catalytic inhibitor aclarubicin and in Topo II-deficient mitoxantrone-resistant variant HL-60/MX2 cells. Together, these results suggest that in emodin-induced DNA DSBs and genotoxicity, stabilization of Topo II-DNA cleavage complexes and inhibition of ATP hydrolysis play an important role. |
| WOS关键词 | SACCHAROMYCES-CEREVISIAE ; INDIVIDUAL CELLS ; MAMMALIAN-CELLS ; COMET ASSAY ; GENOTOXICITY ; ANTHRAQUINONES ; MUTAGENICITY ; GAMMA-H2AX ; ETOPOSIDE ; MECHANISM |
| 资助项目 | National Basic Research Program[2006CB504701] ; National Key Technologies RD Program[2008ZX09305-007] ; National Key Technologies RD Program[2009ZX09501-033] |
| WOS研究方向 | Toxicology |
| 语种 | 英语 |
| 出版者 | OXFORD UNIV PRESS |
| WOS记录号 | WOS:000284432600011 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278712]  |
| 专题 | 药物安全性评价中心 信息中心 药理学第一研究室 |
| 通讯作者 | Ren, Jin |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res,State Key Lab New D, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yan,Luan, Yang,Qi, Xinming,et al. Emodin Triggers DNA Double-Strand Breaks by Stabilizing Topoisomerase II-DNA Cleavage Complexes and by Inhibiting ATP Hydrolysis of Topoisomerase II[J]. TOXICOLOGICAL SCIENCES,2010,118(2):435-443. |
| APA | Li, Yan.,Luan, Yang.,Qi, Xinming.,Li, Ming.,Gong, Likun.,...&Ren, Jin.(2010).Emodin Triggers DNA Double-Strand Breaks by Stabilizing Topoisomerase II-DNA Cleavage Complexes and by Inhibiting ATP Hydrolysis of Topoisomerase II.TOXICOLOGICAL SCIENCES,118(2),435-443. |
| MLA | Li, Yan,et al."Emodin Triggers DNA Double-Strand Breaks by Stabilizing Topoisomerase II-DNA Cleavage Complexes and by Inhibiting ATP Hydrolysis of Topoisomerase II".TOXICOLOGICAL SCIENCES 118.2(2010):435-443. |
入库方式： OAI收割
来源：上海药物研究所
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