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Apoptotic effect of celecoxib dependent upon p53 status in human ovarian cancer cells
Yoo-Cheol Song1, Su-Hyeong Kim, Yong-Sung Juhnn
1Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongun-dong, Chongno-gu, Seoul, 110-744, Korea.
Abstract:
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.
Insights
Celecoxib induces apoptosis in ovarian cancer cells, with greater effect in those with functional p53 protein. The drug
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, induces apoptosis in various cancers.
- The p53 protein is frequently mutated in human tumors, including ovarian cancer, and is crucial for apoptosis and cell cycle regulation.
- Ovarian cancer exhibits a high rate of p53 mutation, correlating with poor prognosis.
Purpose of the Study:
- To investigate the role of functional p53 status in celecoxib-induced apoptosis in ovarian cancer cells.
- To compare the cellular response to celecoxib in ovarian cancer cell lines with differing p53 functional status (null vs. wild-type).
Main Methods:
- Cellular response to celecoxib was assessed in SK-OV3 (null p53) and PA-1 (wild-type p53) ovarian cancer cells.
- Cell proliferation was measured.
- Cell cycle analysis was performed to determine sub-G1 phase percentages.
- Activation of caspases -8, -9, and -3 was evaluated.
Main Results:
- Celecoxib inhibited cell growth more significantly in PA-1 (wild-type p53) cells compared to SK-OV3 (null p53) cells.
- A higher percentage of PA-1 cells entered the sub-G1 phase (60.28%) than SK-OV3 cells (6.69%) after celecoxib treatment.
- Caspase -8, -9, and -3 activation was observed in PA-1 cells but not in SK-OV3 cells.
Conclusions:
- Celecoxib effectively inhibits cell growth and induces apoptosis in human ovarian cancer cells, particularly those with wild-type p53.
- The functional status of p53 influences the apoptotic pathways activated by celecoxib, suggesting involvement of death receptor and mitochondria-mediated pathways.
- Apoptotic effects of celecoxib in ovarian cancer are dependent on the p53 functional status.
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