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Apoptotic Effect of Celecoxib Dependent Upon p53 Status in Human Ovarian Cancer Cells
Author(s) -
SONG YOOCHEOL,
KIM SUHYEONG,
JUHNN YONGSUNG,
SONG YONGSANG
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1397.004
Subject(s) - celecoxib , apoptosis , ovarian cancer , cancer research , cell cycle , programmed cell death , cancer cell , cancer , cell growth , cell , chemistry , biology , medicine , pharmacology , biochemistry
: Celecoxib, a selective cyclooxygenase‐2 (COX‐2) inhibitor, induces the apoptosis in various cancers in COX‐2 dependent and/or independent manners. The p53 protein is mutated in 50% of all human tumors and plays a key role in apoptosis, cell cycle, and the expression of several proteins. In ovarian cancer, the rate of p53 mutation has been shown to be very high and associated with poor prognosis. To explore the importance of functional status of p53 in apoptosis by celecoxib in ovarian cancer cells, the cellular response to celecoxib was determined in SK‐OV3 ovarian cancer cells with null type p53 and PA‐1 with wild‐type p53.Our results showed that celecoxib inhibited cell growth more in PA‐1 than in SK‐OV3. The underlying antiproliferative mechanism may differ between these two cell types dependent upon the functional status of p53, which plays integral roles in regulating cell cycle and survival. Higher sub‐G1 was shown in PA‐1 than in SK‐OV3 in response to celecoxib (PA‐1 versus SK‐OV3; 60.28% versus 6.69%). Caspase ‐8, ‐9, and ‐3 were activated in PA‐1 cells, but not in SK‐OV3 cells. These results suggest that death receptor and mitochondria‐mediated apoptotic pathways may be involved in celecoxib‐induced apoptosis dependent upon the functional status of p53. Our article demonstrated that the celecoxib effectively inhibited cell growth and induced apoptosis in human ovarian cancer cells with wild‐type p53. Thus, apoptotic effect by celecoxib seemed to be different dependent upon the functional status of p53.