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Celecoxib induces apoptosis in cervical cancer cells independent of cyclooxygenase using NF-κB as a possible target

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Authors
Kim, Su-Hyeong; Song, Sang-Hyun; Kim, Sang-Gyun; Chun, Kyung-Soo; Lim, So-Young; Na, Hye-Kyung; Kim, Jae Weon; Surh, Young-Joon; Bang, Yung-Jue; Song, Yong-Sang
Issue Date
2004-09
Citation
Journal of Cancer Research and Clinical Oncology, Vol.130 No.9, pp.551-560
Keywords
COX-2celecoxibapoptosiscaspaseFADDNF-kappa B
Abstract
Purpose. Recently, many studies have shown that celecoxib induces apoptosis in various cancer cells by different mechanisms depending on the cell type. This study examined the apoptotic effect of celecoxib in cervical cancer cells and its mechanism. Methods. Cell viability was measured by MTT assay and apoptosis was examined by DNA fragmentation and flow cytometry. Western blotting and immunoprecipitation were used to explore various mechanisms of celecoxib-induced apoptosis. The activation of NF-kappaB was confirmed by EMSA. Results. Celecoxib induced apoptosis independent of COX-2 activity. This event accompanied the activation of caspase-8 and -9 with Bid cleavage and the loss of mitochondrial membrane potential. The protective effect of caspase-8 and -9 inhibitors on celecoxib-induced apoptosis suggests the importance of caspase-8 and -9 activation in this apoptotic pathway. Fas/FADD-mediated apoptotic pathway was detected only in C33A cells, demonstrated by the immunoprecipitation of Fas-FADD in celecoxib-treated cells and the protective effect of FADD dominant negative mutant. Finally, NF-kappaB appeared to be involved in celecoxib-induced apoptosis, as revealed by increased NF-kB DNA binding activity in a time-dependent manner and attenuation of its proapoptotic effect by N-tosyl-L-phenylalanyl-chloromethyl ketone, an NF-kappaB blocker. Conclusions. These data show that caspase-8 and -9 are involved in the apoptotic effect of celecoxib in cervical cancer cells. This requires the FADD-dependent pathway in a cell type-specific manner. In addition, NF-kappaB may play a key role in celecoxib-induced apoptosis.
ISSN
0171-5216
URI
https://hdl.handle.net/10371/172546
DOI
https://doi.org/10.1007/s00432-004-0567-6
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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