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GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Su-Hyeong | - |
dc.contributor.author | Hwang, Chang-Il | - |
dc.contributor.author | Park, Woong-Yang | - |
dc.contributor.author | Lee, Je-Ho | - |
dc.contributor.author | Song, Yong-Sang | - |
dc.date.accessioned | 2010-01-08T07:58:40Z | - |
dc.date.available | 2010-01-08T07:58:40Z | - |
dc.date.issued | 2006-04-07 | - |
dc.identifier.citation | Carcinogenesis. 2006 Oct;27(10):1961-9. Epub 2006 Apr 5. | en |
dc.identifier.issn | 0143-3334 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16597647 | - |
dc.identifier.uri | https://hdl.handle.net/10371/29006 | - |
dc.description.abstract | Celecoxib, 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.iso | en | en |
dc.publisher | Oxford University Press | en |
dc.subject | Apoptosis/*drug effects | en |
dc.subject | Cyclooxygenase 2 Inhibitors/*pharmacology | en |
dc.subject | Female | en |
dc.subject | Hela Cells | en |
dc.subject | Humans | en |
dc.subject | NF-kappa B/physiology | en |
dc.subject | Pyrazoles/*pharmacology | en |
dc.subject | RNA, Messenger/analysis | en |
dc.subject | RNA, Small Interfering/pharmacology | en |
dc.subject | Signal Transduction | en |
dc.subject | Sulfonamides/*pharmacology | en |
dc.subject | Transcription Factor CHOP/genetics/*physiology | en |
dc.subject | Uterine Cervical Neoplasms/chemistry/*drug therapy/pathology | en |
dc.subject | bcl-2 Homologous Antagonist-Killer Protein/genetics | en |
dc.title | GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 김수형 | - |
dc.contributor.AlternativeAuthor | 황창일 | - |
dc.contributor.AlternativeAuthor | 박웅양 | - |
dc.contributor.AlternativeAuthor | 이제호 | - |
dc.contributor.AlternativeAuthor | 송용상 | - |
dc.identifier.doi | 10.1093/carcin/bgl027 | - |
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