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.

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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