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GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells
Cited 16 time in
Web of Science
Cited 17 time in Scopus
- Authors
- Issue Date
- 2006-04-07
- Publisher
- Oxford University Press
- Citation
- Carcinogenesis. 2006 Oct;27(10):1961-9. Epub 2006 Apr 5.
- Keywords
- Apoptosis/*drug effects ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Female ; Hela Cells ; Humans ; NF-kappa B/physiology ; Pyrazoles/*pharmacology ; RNA, Messenger/analysis ; RNA, Small Interfering/pharmacology ; Signal Transduction ; Sulfonamides/*pharmacology ; Transcription Factor CHOP/genetics/*physiology ; Uterine Cervical Neoplasms/chemistry/*drug therapy/pathology ; bcl-2 Homologous Antagonist-Killer Protein/genetics
- 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.
- ISSN
- 0143-3334 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16597647
https://hdl.handle.net/10371/29006
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