Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase2 alpha by unique interference with its DNA binding and catalytic cycle
文献类型：期刊论文
| 作者 | Li, M.2 ; Miao, Z. -H.2; Chen, Z.1; Chen, Q.2; Gui, M.2; Lin, L. -P.2; Sun, P.3; Yi, Y. -H.3; Ding, J.2
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| 刊名 | ANNALS OF ONCOLOGY
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| 出版日期 | 2010-03 |
| 卷号 | 21期号:3页码:597-607 |
| 关键词 | catalytic cycle DNA damage echinoside A marine-derived anticancer drugs topoisomerase2 inhibitor |
| ISSN号 | 0923-7534 |
| DOI | 10.1093/annonc/mdp335 |
| 文献子类 | Article |
| 英文摘要 | Background: Echinoside A was isolated from sea cucumber. This study demonstrates its anticancer effects and its mechanisms of action. Materials and methods: Anticancer effects of echinoside A were evaluated in vitro and in vivo. TUNEL and DNA fragmentation assays were applied to examine its ability to induce apoptosis. A series of biochemical assays were applied to investigate the inhibition of echinoside A on topoisomerase2 alpha (Top2 alpha). Molecular docking analyses were used to demonstrate the direct interaction between echinoside A and Top2 alpha. Results: Echinoside A inhibited the growth of tumors in mouse models and human prostate carcinoma xenografts in nude mouse models. Echinoside A shows the unique characteristics of inhibiting the noncovalent binding of Top2 alpha to DNA by competing with DNA for the DNA-binding domain of the enzyme and of interfering predominantly with the Top2 alpha-mediated prestrand passage cleavage/religation equilibrium over with the poststrand passage one. These features distinguish echinoside A from other known Top2 alpha inhibitors. As a result, echinoside A induced DNA double-strand breaks in a Top2-dependent manner. Conclusion: Echinoside A targets Top2 alpha by unique interference with the binding of Top2 to DNA and by imparing the Top2-mediated DNA cleavage and religation, exerting potent in vitro and in vivo antitumor activities. |
| WOS关键词 | CLEAVAGE COMPLEXES ; MULTIDRUG-RESISTANCE ; NATURAL-PRODUCTS ; II INHIBITORS ; CANCER-CELLS ; IN-VIVO ; DRUGS ; APOPTOSIS ; DERIVATIVES ; PSAMMAPLIN |
| 资助项目 | National High Technology Research and Development Program of China[2006AA090304] ; National Natural Science Foundation of China[30772588] ; National Natural Science Foundation of China[30721005] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000276045300025 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278956]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 天然药物化学研究室 药物安全性评价中心 |
| 通讯作者 | Ding, J. |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Second Mil Med Univ, Sch Pharm, Res Ctr Marine Drugs, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, M.,Miao, Z. -H.,Chen, Z.,et al. Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase2 alpha by unique interference with its DNA binding and catalytic cycle[J]. ANNALS OF ONCOLOGY,2010,21(3):597-607. |
| APA | Li, M..,Miao, Z. -H..,Chen, Z..,Chen, Q..,Gui, M..,...&Ding, J..(2010).Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase2 alpha by unique interference with its DNA binding and catalytic cycle.ANNALS OF ONCOLOGY,21(3),597-607. |
| MLA | Li, M.,et al."Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase2 alpha by unique interference with its DNA binding and catalytic cycle".ANNALS OF ONCOLOGY 21.3(2010):597-607. |
入库方式： OAI收割
来源：上海药物研究所
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