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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
Kim, Su-Hyeong; Hwang, Chang-Il; Park, Woong-Yang; Lee, Je-Ho; Song, Yong-Sang
Issue Date
2006-04-07
Publisher
Oxford University Press
Citation
Carcinogenesis. 2006 Oct;27(10):1961-9. Epub 2006 Apr 5.
Keywords
Apoptosis/*drug effectsCyclooxygenase 2 Inhibitors/*pharmacologyFemaleHela CellsHumansNF-kappa B/physiologyPyrazoles/*pharmacologyRNA, Messenger/analysisRNA, Small Interfering/pharmacologySignal TransductionSulfonamides/*pharmacologyTranscription Factor CHOP/genetics/*physiologyUterine Cervical Neoplasms/chemistry/*drug therapy/pathologybcl-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

http://hdl.handle.net/10371/29006
DOI
https://doi.org/10.1093/carcin/bgl027
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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