DNA damage, c-myc suppression and apoptosis induced by the novel topoisomerase II inhibitor, salvicine, in human breast cancer MCF-7 cells
文献类型：期刊论文
| 作者 | Lu, HR; Meng, LH ; Huang, M; Zhu, H; Miao, ZH; Ding, J
|
| 刊名 | CANCER CHEMOTHERAPY AND PHARMACOLOGY
 |
| 出版日期 | 2005-03 |
| 卷号 | 55期号:3页码:286-294 |
| 关键词 | salvicine DNA damage apoptosis c-myc p2 promoter p53 |
| ISSN号 | 0344-5704 |
| DOI | 10.1007/s00280-004-0877-z |
| 文献子类 | Article |
| 英文摘要 | Salvicine, a diterpenoid quinone compound, possesses potent in vitro and in vivo antitumor activity. Salvicine is a novel non-intercalative topoisomerase II poison. In this study salvicine induced evident DNA damage, which was further characterized as double-strand breaks mainly in MCF-7 human breast cancer cells. The degree of damage was highly correlated with growth inhibition of MCF-7. Using a PCR-stop assay we demonstrated that this damage was selective. Preferential damage occurred in the p2 promoter region, but not the 3'-end of the protooncogene c-myc. The expression of oncogenes, such as c-myc and c-jun, was additionally investigated. Salvicine induced a dose-dependent decrease in c-myc gene transcription, concomitant with an increase in c-jun expression. Furthermore, reverse-transcription PCR and Western blotting data revealed that salvicine failed to stimulate the mRNA and protein levels of p53 and its downstream targets p21 and bax. The phosphorylation degree of serine 15 of p53, which is thought to be an active form of p53 in response to cellular DNA damage, remained in a steady state. In view of these results, we propose that the downregulation of c-myc resulting from selective damage plays a role in apoptosis signaling. Moreover, salvicine-induced apoptosis in MCF-7 subsequent to DNA damage seems to be mediated through a p53-independent pathway. |
| WOS关键词 | DOWN-REGULATION ; TUMOR-CELLS ; TRANSCRIPTION FACTOR ; GENE-EXPRESSION ; ANTITUMOR DRUGS ; P53 ; REPAIR ; CYTOTOXICITY ; ACTIVATION ; INDUCTION |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000225912900011 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273899]  |
| 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 | Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lu, HR,Meng, LH,Huang, M,et al. DNA damage, c-myc suppression and apoptosis induced by the novel topoisomerase II inhibitor, salvicine, in human breast cancer MCF-7 cells[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2005,55(3):286-294. |
| APA | Lu, HR,Meng, LH,Huang, M,Zhu, H,Miao, ZH,&Ding, J.(2005).DNA damage, c-myc suppression and apoptosis induced by the novel topoisomerase II inhibitor, salvicine, in human breast cancer MCF-7 cells.CANCER CHEMOTHERAPY AND PHARMACOLOGY,55(3),286-294. |
| MLA | Lu, HR,et al."DNA damage, c-myc suppression and apoptosis induced by the novel topoisomerase II inhibitor, salvicine, in human breast cancer MCF-7 cells".CANCER CHEMOTHERAPY AND PHARMACOLOGY 55.3(2005):286-294. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。