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GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells

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dc.contributor.authorKim, Su-Hyeong-
dc.contributor.authorHwang, Chang-Il-
dc.contributor.authorPark, Woong-Yang-
dc.contributor.authorLee, Je-Ho-
dc.contributor.authorSong, Yong-Sang-
dc.date.accessioned2010-01-08T07:58:40Z-
dc.date.available2010-01-08T07:58:40Z-
dc.date.issued2006-04-07-
dc.identifier.citationCarcinogenesis. 2006 Oct;27(10):1961-9. Epub 2006 Apr 5.en
dc.identifier.issn0143-3334 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16597647-
dc.identifier.urihttp://hdl.handle.net/10371/29006-
dc.description.abstractCelecoxib, a selective cyclooxygenase-2 inhibitor, is known to possess anti-inflammatory activity and also induces apoptosis in various types of cancer cells. Here, we examined the molecular mechanism of celecoxib-induced apoptosis in cervical cancer cell lines (HeLa, CaSki and C33A). Screening of a cDNA microarray chip containing 225 different genes revealed that GADD153 (growth arrest and DNA damage inducible gene), a transcription factor involved in apoptosis, showed the strongest differential expression following celecoxib treatment in all three cervical cancer cell lines. Notably, siRNA-induced silencing of GADD153 suppressed celecoxib-induced apoptosis in all three cell lines, and exogenous expression of GADD153 triggered apoptosis in cervical cancer cells in the absence of other apoptotic stimuli. A luciferase reporter gene assay and mRNA stability tests revealed that the expression of GADD153 was regulated at both the transcriptional and post-transcriptional levels following celecoxib treatment. The region between -649 and -249, containing an intact C/EBP-ATF binding site, is required for celecoxib-induced stimulation of GADD153 promoter activity. In terms of signaling pathway, addition of the NF-kappaB inhibitor, N-tosyl-L-phenylalanyl-chloromethyl ketone, had no effect on GADD153 expression levels. Celecoxib treatment induced Bak expression, whereas cell transfected with siGADD153 showed lower levels of celecoxib-induced Bak upregulation. These novel findings collectively suggest that GADD153 may play a key role in celecoxib-induced apoptosis in cervical cancer cells by regulating the expression of proapoptotic proteins such as Bak.en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.subjectApoptosis/*drug effectsen
dc.subjectCyclooxygenase 2 Inhibitors/*pharmacologyen
dc.subjectFemaleen
dc.subjectHela Cellsen
dc.subjectHumansen
dc.subjectNF-kappa B/physiologyen
dc.subjectPyrazoles/*pharmacologyen
dc.subjectRNA, Messenger/analysisen
dc.subjectRNA, Small Interfering/pharmacologyen
dc.subjectSignal Transductionen
dc.subjectSulfonamides/*pharmacologyen
dc.subjectTranscription Factor CHOP/genetics/*physiologyen
dc.subjectUterine Cervical Neoplasms/chemistry/*drug therapy/pathologyen
dc.subjectbcl-2 Homologous Antagonist-Killer Protein/geneticsen
dc.titleGADD153 mediates celecoxib-induced apoptosis in cervical cancer cellsen
dc.typeArticleen
dc.contributor.AlternativeAuthor김수형-
dc.contributor.AlternativeAuthor황창일-
dc.contributor.AlternativeAuthor박웅양-
dc.contributor.AlternativeAuthor이제호-
dc.contributor.AlternativeAuthor송용상-
dc.identifier.doi10.1093/carcin/bgl027-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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