Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/68840
DC FieldValueLanguage
dc.contributor.authorYang, T.Y.en_US
dc.contributor.authorChang, G.C.en_US
dc.contributor.authorChen, K.C.en_US
dc.contributor.authorHung, H.W.en_US
dc.contributor.authorHsu, K.H.en_US
dc.contributor.authorSheu, G.T.en_US
dc.contributor.authorHsu, S.L.en_US
dc.date2011zh_TW
dc.date.accessioned2014-06-11T05:57:24Z-
dc.date.available2014-06-11T05:57:24Z-
dc.identifier.issn0014-2999zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/68840-
dc.description.abstractPemetrexed, a multitargeted antifolate with the ability to inhibit several enzymes involved in purine and pyrimidine syntheses, has demonstrated clinical activity in non-small cell lung cancer cells, as well as in a broad array of other solid tumors. In this study, we show that inducing cell cycle S-phase arrest and apoptosis in human lung adenocarcinoma A549 cells with pemetrexed is associated with increased cyclin-A and cyclin-dependent kinase 2 (Cdk2) protein and Cdk2/cyclin-A kinase activity. Knockdown of cyclin-A using small interfering RNA (siRNA), and inhibiting Cdk2 activity with flavopiridol, strikingly reduced S-phase arrest and apoptosis. Moreover, pemetrexed induced sustained activation of extracellular signal-regulated kinase1/2 (ERK1/2). Knockdown of ERK1/2 using specific siRNA, as well as known inhibitors (PD98059 and U0126), effectively suppressed the expression of cyclin-A and Cdk2, and reduced S-phase arrest and apoptosis induced by pemetrexed. These data provide the first evidence that pemetrexed-induced S-phase arrest and apoptosis is associated with an increase in Cdk2 and cyclin-A expression and activation, which is ERK-dependent and upstream of caspase-3. Our findings suggest that the ERK-mediated Cdk2/cyclin-A signaling pathway is an important regulator of pemetrexed-induced S-phase arrest and apoptotic cell death. (C) 2011 Elsevier B.V. All rights reserved.en_US
dc.language.isoen_USzh_TW
dc.relationEuropean Journal of Pharmacologyen_US
dc.relation.ispartofseriesEuropean Journal of Pharmacology, Volume 663, Issue 1-3, Page(s) 17-26.en_US
dc.relation.urihttp://dx.doi.org/10.1016/j.ejphar.2011.04.057en_US
dc.subjectPemetrexeden_US
dc.subjectS phase arresten_US
dc.subjectApoptosisen_US
dc.subjectERKen_US
dc.subjectCDK2en_US
dc.subjectCyclin-Aen_US
dc.subjectmultitargeted antifolate ly231514en_US
dc.subjecthuman tumor xenograftsen_US
dc.subjectdna-damageen_US
dc.subjectcycle arresten_US
dc.subjectregulated kinaseen_US
dc.subjectdeathen_US
dc.subjectchemotherapyen_US
dc.subjectcisplatinen_US
dc.subjectregimensen_US
dc.subjectatmen_US
dc.titleSustained activation of ERK and Cdk2/cyclin-A signaling pathway by pemetrexed leading to S-phase arrest and apoptosis in human non-small cell lung cancer A549 cellsen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1016/j.ejphar.2011.04.057zh_TW
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en_US-
item.fulltextno fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
Appears in Collections:期刊論文
Show simple item record
 

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.