Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells
文献类型：期刊论文
| 作者 | Miao, ZH; Tang, T; Zhang, YX; Zhang, JS; Ding, J
|
| 刊名 | INTERNATIONAL JOURNAL OF CANCER
 |
| 出版日期 | 2003-08-10 |
| 卷号 | 106期号:1页码:108-115 |
| 关键词 | salvicine MDR apoptosis K562/A02 cells P-gp |
| ISSN号 | 0020-7136 |
| DOI | 10.1002/ijc.11174 |
| 文献子类 | Article |
| 英文摘要 | Salvicine, a novel topoisomerase II inhibitor and a diterpenoid quinone compound, exerts potent in vitro and in vivo antitumor effects. In our study, we show that salvicine effectively kills multidrug-resistant (MDR) sublines, such as K562/A02, KB/VCR and MCF-7/ADR, and parental K562, KB and MCF-7 cell lines to an equivalent degree. These cytotoxic activities of salvicine were much more potent than those of Several classical anticancer drugs (average resistance factor: 1.42 for salvicine vs. 344.35, 233.19 and 71.22 for vincristine, doxorubicin and etoposide, respectively). Flow cytometry and DNA agarose gel electrophoresis demonstrated that salvicine induced similar levels of apoptosis in MDR K562/A02 and parental cells. The compound activated caspase-1 and -3 (but not caspase-8) and increased the ratio of box to bcl-2 mRNA via reduction of bcl-2 mRNA expression in the same cells. Furthermore, salvicine induced the downregulation of mdr-1 gene and P-gp expression but had no effect on MRP and LRP gene expression in MDR K562/A02 cells. These results suggest that the reduction of mdr-1 and bcl-2 expression by salvicine possibly contributes to its cytotoxicity and apoptotic induction in this system. The effectiveness, broad-spectrum activity and possibly novel mechanism of killing MDR tumor cells in vitro of salvicine signify promising in vivo and clinical activity. The novel chemical structure of this compound further implies a role for salvicine in future MDR tumor therapy. (C) 2003 Wiley-Liss, Inc. |
| WOS关键词 | BREAST-CANCER-CELLS ; P-GLYCOPROTEIN ; LEUKEMIA-CELLS ; MYELOID-LEUKEMIA ; C-MYC ; PROTEIN ; ACTIVATION ; DOXORUBICIN ; CASPASE-3 ; EFFLUX |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000183723900016 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274198]  |
| 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, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Dept Phytochem, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Miao, ZH,Tang, T,Zhang, YX,et al. Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells[J]. INTERNATIONAL JOURNAL OF CANCER,2003,106(1):108-115. |
| APA | Miao, ZH,Tang, T,Zhang, YX,Zhang, JS,&Ding, J.(2003).Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells.INTERNATIONAL JOURNAL OF CANCER,106(1),108-115. |
| MLA | Miao, ZH,et al."Cytotoxicity, apoptosis induction and downregulation of MDR-1 expression by the anti-topoisomerase II agent, salvicine, in multidrug-resistant tumor cells".INTERNATIONAL JOURNAL OF CANCER 106.1(2003):108-115. |
入库方式： OAI收割
来源：上海药物研究所
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