https://scholars.lib.ntu.edu.tw/handle/123456789/564776
標題: | Tubulin-binding agents down-regulate matrix metalloproteinase-2 and -9 in human hormone-refractory prostate cancer cells - A critical role of Cdk1 in mitotic entry | 作者: | Chang W.-L. Yu C.-C. Chen C.-S. JIH-HWA GUH |
關鍵字: | Cdk1; Matrix metalloproteinase; Mitotic entry and exit; Synchronization; Tubulin-binding agent | 公開日期: | 2015 | 卷: | 94 | 期: | 1 | 起(迄)頁: | 12-21 | 來源出版物: | Biochemical Pharmacology | 摘要: | Tubulin is an important target for anticancer therapy. Taxanes and vinca alkaloids are two groups of tubulin-binding agents in cancer chemotherapy. Besides tubulin binding, these groups of agents can also down-regulate protein levels of matrix metalloproteinase (MMP)-2 and -9, two important cancer-associated zinc-dependent endopeptidases in invasion and metastasis. However, the mechanism of action waits to be explored. In this study, protein levels but not mRNA expressions of MMP-2 and -9 were down-regulated by paclitaxel (a microtubule-stabilization agent), vincristine and evodiamine (two tubulin-depolymerization agents). These agents induced an increase of protein expression of cyclin B1, MPM2 (mitosis-specific phosphoprotein) and polo-like kinase (PLK) 1 phosphorylation. The data showed a negative relationship between the levels of mitotic proteins and MMP-2 and -9 expressions. MG132 (a specific cell-permeable proteasome inhibitor) blocked mitotic entry and arrested cell cycle at G2 phase, preventing down-regulation of MMP-2 and -9. Cell cycle synchronization experiments by thymidine block or nocodazole treatment showed that mitotic exit inhibited the down-regulation of MMP-2 and -9, confirming negative relationship between cell mitosis and protein levels of MMP-2 and -9 expressions. Cyclin-dependent kinase (Cdk) 1 is a key kinase in mitotic entry. Knockdown of Cdk1 almost completely inhibited the down-regulation of MMP-2 and -9 induced by tubulin-binding agents. In conclusion, the data suggest that mitotic entry and Cdk1 plays a central role in down-regulation of MMP-2 and -9 protein expressions. Tubulin-binding agents cause mitotic arrest and Cdk1 activation, which may contribute largely to the down-regulation of both MMP-2 and -9 expressions. ? 2015 Elsevier Inc. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84922716209&doi=10.1016%2fj.bcp.2015.01.005&partnerID=40&md5=48dc3a81adad400da34178c26060c94c https://scholars.lib.ntu.edu.tw/handle/123456789/564776 |
ISSN: | 62952 | DOI: | 10.1016/j.bcp.2015.01.005 | SDG/關鍵字: | benzyloxycarbonylleucylleucylleucinal; cyclin B1; cyclin dependent kinase 1; evodiamine; gelatinase A; gelatinase B; messenger RNA; MPM2 protein; nocodazole; paclitaxel; polo like kinase 1; protein; thymidine; unclassified drug; vincristine; antineoplastic agent; benzyloxycarbonylleucyl-leucyl-leucine aldehyde; CDK1 protein, human; cell cycle protein; cyclin B1; cyclin dependent kinase; evodiamine; gelatinase A; gelatinase B; leupeptin; nocodazole; oncoprotein; paclitaxel; polo-like kinase 1; protein serine threonine kinase; quinazoline derivative; small interfering RNA; tubulin modulator; vincristine; Article; castration resistant prostate cancer; cell cycle arrest; cell cycle G2 phase; cell synchronization; concentration (parameters); controlled study; down regulation; enzyme activation; gene silencing; human; human cell; male; mitosis; mitosis inhibition; priority journal; protein expression; protein function; protein phosphorylation; agonists; antagonists and inhibitors; apoptosis; drug effects; drug resistance; G2 phase cell cycle checkpoint; gene expression regulation; genetics; metabolism; mitosis; signal transduction; tumor cell line; Antineoplastic Agents; Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Cyclin B1; Cyclin-Dependent Kinases; Drug Resistance, Neoplasm; G2 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Humans; Leupeptins; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mitosis; Nocodazole; Paclitaxel; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Quinazolines; RNA, Small Interfering; Signal Transduction; Tubulin Modulators; Vincristine |
顯示於: | 藥學系 |
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