Gambogic acid inhibits the catalytic activity of human topoisomerase II alpha by binding to its ATPase domain
文献类型：期刊论文
| 作者 | Qin, Yuxin; Meng, Linghua ; Hu, Chaoxin; Duan, Wenhu; Zuo, Zhili; Lin, Liping; Zhang, Xiongwen; Ding, Jian
|
| 刊名 | MOLECULAR CANCER THERAPEUTICS
 |
| 出版日期 | 2007-09 |
| 卷号 | 6期号:9页码:2429-2440 |
| ISSN号 | 1535-7163 |
| DOI | 10.1158/1535-7163.MCT-07-0147 |
| 文献子类 | Article |
| 英文摘要 | This study is intended to characterize the cellular target of gambogic acid (GA), a natural product isolated from the gamboge resin of Garcinia hurburyi tree, which possesses potent in vitro and in vivo antitumor activities. The antiproliferative activity of GA was further confirmed here in a panel of human tumor cells and multidrug-resistant cells. We found that GA significantly inhibited the catalytic activity of topoisomerase (Topo) II and, to a comparatively less extent, of Topo I, without trapping and stabilizing covalent topoisomerase-DNA cleavage complexes. Down-regulation of Topo II alpha but not Topo I and Topo II beta, reduced GA-induced apoptosis and the phosphorylation of c-Jun, and restored cell proliferation upon GA treatment. Moreover, GA antagonized etoposide-induced DNA damage and abrogated the antiproliferative activity of etoposide, whereas it did not affect camptothecin-induced DNA damage. By dissecting the actions of GA on the individual steps of Topo II alpha catalytic cycle, we found that GA inhibited DNA cleavage and ATP hydrolysis. Moreover, GA directly bound to the ATPase domain of II alpha, and may share common binding sites with ATP. The results reported here show that GA exerts its antiproliferative effect by inhibiting the catalytic activity Topo II alpha. They also indicate that GA inhibits Topo II alpha-mediated DNA cleavage and modulate the activity of Topo II poisons, which provide rationale for further clinical evaluation of GA. |
| WOS关键词 | MEDIATED DNA CLEAVAGE ; TRANSCRIPTASE MESSENGER-RNA ; GYRASE-B PROTEIN ; SEQUENCE SPECIFICITY ; DRUG-SENSITIVITY ; CANCER-THERAPY ; CELLS ; ENZYME ; CYTOTOXICITY ; ETOPOSIDE |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000249716200007 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273170]  |
| 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 |
| 通讯作者 | Ding, Jian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Phytochem, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qin, Yuxin,Meng, Linghua,Hu, Chaoxin,et al. Gambogic acid inhibits the catalytic activity of human topoisomerase II alpha by binding to its ATPase domain[J]. MOLECULAR CANCER THERAPEUTICS,2007,6(9):2429-2440. |
| APA | Qin, Yuxin.,Meng, Linghua.,Hu, Chaoxin.,Duan, Wenhu.,Zuo, Zhili.,...&Ding, Jian.(2007).Gambogic acid inhibits the catalytic activity of human topoisomerase II alpha by binding to its ATPase domain.MOLECULAR CANCER THERAPEUTICS,6(9),2429-2440. |
| MLA | Qin, Yuxin,et al."Gambogic acid inhibits the catalytic activity of human topoisomerase II alpha by binding to its ATPase domain".MOLECULAR CANCER THERAPEUTICS 6.9(2007):2429-2440. |
入库方式： OAI收割
来源：上海药物研究所
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