SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor
文献类型：期刊论文
| 作者 | Yang, Fan; Chen, Yi ; Duan, Wenhu; Zhang, Chao; Zhu, Hong; Ding, Jian
|
| 刊名 | INTERNATIONAL JOURNAL OF CANCER
 |
| 出版日期 | 2006-09-01 |
| 卷号 | 119期号:5页码:1184-1193 |
| 关键词 | SH-7 shikonin topoisomerase II inhibitor antitumor mitochondria |
| ISSN号 | 0020-7136 |
| DOI | 10.1002/ijc.21943 |
| 文献子类 | Article |
| 英文摘要 | 1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enylfuran-2-caroxylate (SH-7), a new naphthoquinone compound, derived from shikonin, exhibited obvious inhibitory actions on topoisomerase II (Topo II) and topoisomerase I (Topo I), which were stronger than its mother compound shikonin. Notably, the SH-Ts inhibitory potency on Topo II was much stronger than that on Topo I. In addition, SH-7 significantly stabilized Topo II-DNA cleavable complex and elevated the expression of phosphorylated-H2AX. The in vitro cell-based investigation demonstrated that SH-7 displayed wide cytotoxicity in diversified cancer cell lines with the mean IC50 value of 7.75 mu M. One important finding is SH-7 displayed significant cytotoxicity in the 3 MDR cell lines, with an average IC50 value nearly equivalent to that of the corresponding parental cell lines. The average resistance factor (RF) of SH-7 was 1.74, which was much lower than those of reference drugs VP-16 (RF 145.92), ADR (RF 105.97) and VCR (RF 197.39). Further studies illustrated that SH-7 had the marked apoptosis-inducing function on leukemia HL-60 cells, which was validated to be of mitochondria-dependence. The in vivo experiments showed that SH-7 had inhibitory effects on S-180 sarcoma implanted to mice, SMMC-7721, BEL-7402 human hepatocellular carcinoma and PC-3 human prostate cancer implanted to nude mice. Taken together, these results suggest that SH-7 induces DSBs as a Topo II inhibitor, which was crucial to activate the apoptotic process, and subsequently accounts for its both in vitro and in vivo antitumor activities. The well-defined Topo II inhibitory activity, antitumor effects particularly with its obvious anti-MDR action, better solubility and less toxicity make SH-7 as a potential antitumor drug candidate for further research and development. (c) 2006 Wiley-Liss, Inc. |
| WOS关键词 | DOUBLE-STRAND BREAKS ; MULTIDRUG-RESISTANCE ; INDUCED APOPTOSIS ; LITHOSPERMUM-ERYTHRORHIZON ; DNA TOPOISOMERASES ; CELL-DEATH ; IN-VIVO ; CYTOTOXICITY ; EXPRESSION ; INGREDIENT |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000239287800028 |
| 出版者 | WILEY-LISS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273506]  |
| 专题 | 药物化学研究室 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 药理学第一研究室 |
| 通讯作者 | Duan, Wenhu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Fan,Chen, Yi,Duan, Wenhu,et al. SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor[J]. INTERNATIONAL JOURNAL OF CANCER,2006,119(5):1184-1193. |
| APA | Yang, Fan,Chen, Yi,Duan, Wenhu,Zhang, Chao,Zhu, Hong,&Ding, Jian.(2006).SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor.INTERNATIONAL JOURNAL OF CANCER,119(5),1184-1193. |
| MLA | Yang, Fan,et al."SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor".INTERNATIONAL JOURNAL OF CANCER 119.5(2006):1184-1193. |
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。