11,11'-dideoxy-verticillin: A natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity
文献类型：期刊论文
| 作者 | Zhang, YX; Chen, Y ; Guo, XN; Zhang, XW; Zhao, WM; Zhong, L; Zhou, J; Xi, Y; Lin, LP; Ding, J
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| 刊名 | ANTI-CANCER DRUGS
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| 出版日期 | 2005-06 |
| 卷号 | 16期号:5页码:515-524 |
| 关键词 | 11,11'-dideoxy-verticillin epidermal growth factor receptor vascular endothelial growth factor receptor-1 Erk1/2 anti-tumor |
| ISSN号 | 0959-4973 |
| DOI | 10.1097/00001813-200506000-00007 |
| 文献子类 | Article |
| 英文摘要 | 11,11'-Dideoxy-verticillin, a compound of the novel epidithiodioxopiprazine structural class, is isolated from the traditional Chinese medicinal herb Shiraia bambusicola. The present study demonstrated for the first time that 11,11'-dideoxy-verticillin has potent tyrosine kinase-inhibitory and anti-tumor activities. In the cell-free ELISA tyrosine kinase assay, 11,11'-dideoxy-verticillin significantly inhibited the activities of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1 (VEGFR-1/Flt-1) and human epidermal growth factor receptor-2 (HER2/ErbB-2), with relative specificity on EGFR and VEGFR-1 with IC(50)s of 0.136 +/- 0.109 and 1.645 +/- 0.885 nM, respectively. Exposure of 11,11'-dideoxy-verticillin for 1 h to EGFR-overexpressed MDA-MB-468 human breast carcinoma cells and HER2-overexpressed SK-OV-3 human ovarian adenocarcinoma cells resulted in obvious inhibition of EGF-induced phosphorylation of EGFR and HER2. In addition, 11,11'-dideoxy-verticillin also inhibited the EGF-induced phosphorylation of Erk1/2, but had no effect on the phosphorylation of AKT in both tumor cell lines. Moreover, 11,11'-dideoxy-verticillin has potent anti-tumor activity. In vitro cytotoxicity assay showed that 11,11'-dideoxy-verticillin potently inhibited the proliferation of four human breast tumor cell lines with an average IC50 value of 0.2 mu M. In vivo, 11,11'-dideoxy-verticillin exhibited remarkable efficacy against mice sarcoma 180 and hepatoma 22 after daily i.p. administration of 0.5 or 0.75 mg/kg with inhibition rates ranging from 45.0 to 72.4%. Treated with 11,11'-dideoxy-verticillin at 0.5-2.0 mu M for 36h, MB-MB-468 cells exhibited significant apoptotic morphological changes. At low concentrations (0.0625-0.5 mu M) for 24 h, 11,11'-dideoxy-verticillin induced a dose-dependent accumulation of MDA-MB-468 cells in the G(2)/M phase of the cell cycle. These results indicate that 11,11'-dideoxy-verticillin is a naturally derived growth factor receptor tyrosine kinase inhibitor with potent anti-tumor activity. Anti-Cancer Drugs 16:515-524 (c) 2005 Lippincott Williams & Wilkins. |
| WOS关键词 | CELL LUNG-CANCER ; PHASE-II TRIAL ; GEFITINIB ; THERAPY ; PATHWAY ; DRUGS |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000229224300007 |
| 出版者 | LIPPINCOTT WILLIAMS & WILKINS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273860]  |
| 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, J |
| 作者单位 | 1.Chinese Acad Sci, Div Anti Tumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China 2.Chinese Acad Sci, Div Anti Tumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med,Inst Biol Sci,Dept Phytoche, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, YX,Chen, Y,Guo, XN,et al. 11,11'-dideoxy-verticillin: A natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity[J]. ANTI-CANCER DRUGS,2005,16(5):515-524. |
| APA | Zhang, YX.,Chen, Y.,Guo, XN.,Zhang, XW.,Zhao, WM.,...&Ding, J.(2005).11,11'-dideoxy-verticillin: A natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity.ANTI-CANCER DRUGS,16(5),515-524. |
| MLA | Zhang, YX,et al."11,11'-dideoxy-verticillin: A natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity".ANTI-CANCER DRUGS 16.5(2005):515-524. |
入库方式： OAI收割
来源：上海药物研究所
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