P38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4
文献类型：期刊论文
| 作者 | Quan, Haitian ; Xu, Yongping; Lou, Liguang
|
| 刊名 | INTERNATIONAL JOURNAL OF CANCER
 |
| 出版日期 | 2008-04-15 |
| 卷号 | 122期号:8页码:1730-1737 |
| 关键词 | combretastatin A4 mitogen-activated protein kinase p38 MAPK vascular disrupting agent microtubule |
| ISSN号 | 0020-7136 |
| DOI | 10.1002/ijc.23262 |
| 文献子类 | Article |
| 英文摘要 | Combretastatin A4 (CA4) is a novel vascular disrupting agent that has promising clinical efficacy because of its ability to inhibit microtubule assembly and subsequently disrupt tumor blood How. In this study, we demonstrate that mitogen-activated protein kinases (MAPKs) are critically involved in the cytotoxicity of CA4. CA4 stimulates both extracellular signal-regulated kinases (ERK1/2) and p38 MAPK in the BEL-7402 hepatocellular carcinoma cell line in a time- and dose-dependent manner. This stimulation is a result of CA4-induced microtubule disassembly, which is a reversible process. Reversibility of microtubule disassembly is evidenced by the ability of disassembled microtubules to reassemble just a few hours after CA4 treatment. p38 MAPK, but not ERK1/2, contributes to this microtubule reassembly following CA4 exposure, and only inhibition of p38 MAPK, but not ERK1/2, synergistically enhances CA4-induced G(2)/M cell cycle arrest. Consistent with this, p38 MAPK inhibitors such as SB203580 and SB202190 also synergistically enhance the cytotoxicity of CA4 in cells where p38 MAPK is activated by CA4. This enhancement appears to be specific for CA4 because the cytotoxicity of other microtubule-targeted agents such as paclitaxel, vinorelbine and colchicine was not affected by p38 MAPK inhibitors. These data indicate that p38 MAPK is a potential anticancer target and that the combination of CA4 with p38 MAPK inhibitors may be a novel and promising strategy for cancer therapy. (c) 2007 Wiley-Liss, Inc. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; HUMAN ENDOTHELIAL-CELLS ; SOLID TUMOR-THERAPY ; INDUCED APOPTOSIS ; A-4 PHOSPHATE ; A4 PHOSPHATE ; CARCINOMA-CELLS ; MITOTIC ARREST ; CANCER CELLS ; INHIBITOR |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000254068300009 |
| 出版者 | WILEY-LISS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272939]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Lou, Liguang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Quan, Haitian,Xu, Yongping,Lou, Liguang. P38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4[J]. INTERNATIONAL JOURNAL OF CANCER,2008,122(8):1730-1737. |
| APA | Quan, Haitian,Xu, Yongping,&Lou, Liguang.(2008).P38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4.INTERNATIONAL JOURNAL OF CANCER,122(8),1730-1737. |
| MLA | Quan, Haitian,et al."P38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4".INTERNATIONAL JOURNAL OF CANCER 122.8(2008):1730-1737. |
入库方式： OAI收割
来源：上海药物研究所
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