A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule
文献类型：期刊论文
| 作者 | Liu, Zu-long2; Tian, Wei3; Wang, Yong1; Kuang, Shan2; Luo, Xiao-min1 ; Yu, Qiang2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2012-02 |
| 卷号 | 33期号:2页码:261-270 |
| 关键词 | MPSP-001 sulfonamide anticancer drug microtubules tubulin mitotic spindle drug resistance drug synergism |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2011.156 |
| 文献子类 | Article |
| 英文摘要 | Aim: To evaluate the anti-cancer effects of a new sulfonamide derivative, 2-(N-(3-chlorophenyl)-4-methoxyphenylsulfonamido)-N-hydroxypropanamide (MPSP-001). Methods: Human cancer cell lines (HepG2, THP-1, K562, HGC-27, SKOV3, PANC-1, SW480, Kba, HeLa, A549, MDA-MB-453, and MCF-7) were examined. The cytotoxicity of MPSP-001 was evaluated using the WST-8 assay. Cell cycle distribution was examined with flow cytometry. Mitotic spindle formation was detected using immunofluorescence microscopy. Apoptosis-related proteins were examined with Western blot using specific phosphorylated protein antibodies. Competitive tubulin-binding assay was performed to test whether the compound competitively bound to the colchicine site. Molecular docking was performed to explore the possible binding conformation. Results: MPSP-001 potently inhibited the growth of the 12 different types of human cancer cells with the IC50 values ranging from 1.9 to 15.7 mu mol/L. The compound exerted potent inhibition on the drug-resistant Kb/VCR and MCF-7/ADR cells, as on Kba and MCF-7 cells. In HeLa, HGC-27, A549, and other cells, the compound (5 mu mol/L) caused cell cycle arrest at the G(2)/M phase, and subsequently induced cell apoptosis. In Hela cells, it prevented the mitotic spindle formation. Furthermore, the compound dose-dependently inhibited polymerization of tubulin in vitro, and directly bound to the colchicine-site of beta-tubulin. Molecular docking predicted that the compound may form two hydrogen bonds to the binding pocket. The compound showed synergistic effects with colchicine and taxol in blocking mitosis of HeLa cells. Conclusion: MPSP-001 shows a broad-spectrum of anti-tumor efficacy in vitro and represents a novel structure with anti-microtubule activity. |
| WOS关键词 | PHASE-I ; ANTITUMOR-ACTIVITY ; ANTICANCER AGENT ; DRUG-RESISTANCE ; SOLID TUMORS ; BINDING ; APOPTOSIS ; TUBULIN ; E7070 ; COLCHICINE |
| 资助项目 | National Natural Science Foundation of China[30672481] ; National Natural Science Foundation of China[30771097] ; National Natural Science Foundation of China[90713029] ; National Natural Science Foundation of China[30828018] ; Shanghai Science and Technology Research[08DZ1971403] ; China Ministry of Science and Technology[2008ZX10002-020] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09301-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China[2009ZX09103-064] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4437497 |
| WOS记录号 | WOS:000300255400018 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278200]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Yu, Qiang |
| 作者单位 | 1.Chinese Acad Sci, Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 3.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Liu, Zu-long,Tian, Wei,Wang, Yong,et al. A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule[J]. ACTA PHARMACOLOGICA SINICA,2012,33(2):261-270. |
| APA | Liu, Zu-long,Tian, Wei,Wang, Yong,Kuang, Shan,Luo, Xiao-min,&Yu, Qiang.(2012).A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule.ACTA PHARMACOLOGICA SINICA,33(2),261-270. |
| MLA | Liu, Zu-long,et al."A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule".ACTA PHARMACOLOGICA SINICA 33.2(2012):261-270. |
入库方式： OAI收割
来源：上海药物研究所
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