Full metadata record
DC FieldValueLanguage
dc.contributor.authorTsai, Chih-Chienen_US
dc.contributor.authorLiu, Huei-Fangen_US
dc.contributor.authorHsu, Kai-Chengen_US
dc.contributor.authorYang, Jinn-Moonen_US
dc.contributor.authorChen, Chinpiaoen_US
dc.contributor.authorLiu, Kuang-Kaien_US
dc.contributor.authorHsu, Tzu-Shengen_US
dc.contributor.authorChao, Jui-I.en_US
dc.date.accessioned2014-12-08T15:11:50Z-
dc.date.available2014-12-08T15:11:50Z-
dc.date.issued2011-04-01en_US
dc.identifier.issn0006-2952en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.bcp.2011.01.009en_US
dc.identifier.urihttp://hdl.handle.net/11536/9081-
dc.description.abstractThe 5,8-quinolinediones are precursors for producing multiple types of bioactive products. In this study, we investigated a new compound derived from 5,8-quinolinediones, 7-chloro-6-piperidin-1-yl-quinoline-5,8-dione (designated as PT-262), which markedly induced cytoskeleton remodeling and migration inhibition in lung carcinoma cells. Comparison with various cytoskeleton inhibitors, including paclitaxel, colchicine and phallacidin, the cell morphology following treatment with PT-262 was similar to phallacidin on the cell elongation and abnormal actin polymerization. However, PT-262 did not directly bind to actin filaments. ROCK (Rho-associated coiled-coil forming protein kinase) is a downstream effector of RhoA to mediate the phosphorylation of myosin light chain (MLC) and cytoskeleton reorganization. The RhoA-ROCK-MLC pathway has been shown to promote cancer cell migration and metastasis. Interestingly. PT-262 was more effective on inhibiting ROCK kinase activities than specific ROCK inhibitors Y-27632 and H-1152. PT-262 induced cytoskeleton remodeling and migration inhibition in A549 lung carcinoma cells. The total MLC and phosphorylated MLC proteins and stress fibers were blocked after treatment with PT-262. Nonetheless, the RhoA protein and GTPase activity were not altered by PT-262. A computational model suggests that PT-262 interacts with the ATP-binding site of ROCK protein. Together, these findings demonstrate that PT-262 is a new ROCK inhibitor. (C) 2011 Elsevier Inc. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectPT-262en_US
dc.subjectROCKen_US
dc.subjectCell migrationen_US
dc.subjectCytoskeletonen_US
dc.subjectLung canceren_US
dc.title7-Chloro-6-piperidin-1-yl-quinoline-5,8-dione (PT-262), a novel ROCK inhibitor blocks cytoskeleton function and cell migrationen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.bcp.2011.01.009en_US
dc.identifier.journalBIOCHEMICAL PHARMACOLOGYen_US
dc.citation.volume81en_US
dc.citation.issue7en_US
dc.citation.spage856en_US
dc.citation.epage865en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.department生物資訊及系統生物研究所zh_TW
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000288824000004-
dc.citation.woscount2-
Appears in Collections:Articles


Files in This Item:

  1. 000288824000004.pdf

If it is a zip file, please download the file and unzip it, then open index.html in a browser to view the full text content.