Journal Article

GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells

Su-Hyeong Kim, Chang-Il Hwang, Woong-Yang Park, Je-Ho Lee and Yong-Sang Song

in Carcinogenesis

Volume 27, issue 10, pages 1961-1969
ISSN: 0143-3334
Published online April 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl027
GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells

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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-κB 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.

Journal Article.  4648 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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