S-Space College of Medicine/School of Medicine (의과대학/대학원) Obstetrics & Gynecology (산부인과전공) Journal Papers (저널논문_산부인과학전공)
GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells
- Kim, Su-Hyeong; Hwang, Chang-Il; Park, Woong-Yang; Lee, Je-Ho; Song, Yong-Sang
- Issue Date
- Oxford University Press
- Carcinogenesis. 2006 Oct;27(10):1961-9. Epub 2006 Apr 5.
- 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
- 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.
- 0143-3334 (Print)
- Files in This Item: There are no files associated with this item.