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.
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http://dx.doi.org/10.1196/annals.1397.004 | DOI Listing |
Cancer Res Commun
January 2025
Indiana University School of Medicine, Bloomington, IN, United States.
Ovarian cancer is a deadly gynecological disease with frequent recurrence. Current treatments for patients include platinum-based therapy regimens with PARP inhibitors specific for HR-deficient high-grade serous ovarian cancers (HGSOCs). Despite initial effectiveness, patients inevitably develop disease progression as tumor cells acquire resistance.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
Department of Molecular and Biotechnology, Atomic Energy Commission of Syria (AECS), Syria.
Ovarian cancer is a common and lethal malignancy among women, whereas chemoresistance is one of the major challenges to its treatment and prognosis. Chemoresistance is a multifactorial phenomenon, involving various mechanisms that collectively modify the cell's response to treatment. Among the changes that arise in cells after acquiring chemoresistance is miRNA dysregulation.
View Article and Find Full Text PDFWe recently reported on the development of a unique cancer-targeting peptide called NAF-1 (derived from CISD2/NAF-1). NAF-1 selectively permeates the plasma membrane (PM) of cancer cells, but not healthy cells, causing the activation of apoptotic and ferroptotic cell death pathways specifically in cancer cells. NAF-1 also targets and shrinks human breast and ovarian cancer tumors in a xenograft mice model system without any apparent side effects.
View Article and Find Full Text PDFDrug Dev Res
February 2025
Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, China.
Ovarian cancer is the seventh most common lethal tumor among women in the world. FOXM1 is a transcription factor implicated in the initiation and progression of ovarian cancer by regulating key oncogenic genes. The role of regulatory regions in regulating the expression of FOXM1 in ovarian cancer is not completely clarified.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
February 2025
Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
TWIST1 is aberrantly expressed in ovarian cancer (OC). MFAP2 is a downstream target of TWIST1, and we previously found MFAP2 facilitated OC development by activating FOXM1/β-catenin. We planned to investigate the mechanisms of TWIST1 in OC.
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