title: Celecoxib Enhances the Chemotherapeutic Response of Cisplatin and TNF-α in SiHa Cells through Reactive Oxygen Species-Mediated Mitochondrial Pathway.
abstract: 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 effect of the selective COX-2 inhibitor celecoxib on cisplatin and TNF-α cytotoxicity and studied the role of mitochondria in the induction of apoptosis in the human cervical carcinoma SiHa cells. Apoptosis was detected by flow cytometry. The protein expression of Bcl-2, Bcl-XL, Bax, cytochrome c and AIF was analyzed by Western Blotting. The mRNA level of anti-oxidant enzymes was quantitated by RT-PCR. Priming SiHa cells with celecoxib increased the cisplatin-induced apoptosis by 20.56% and priming with celecoxib increased the TNF-α induced apoptosis by 22.07%. This was accompanied by downregulation of Bcl-XL and Bcl-2 and upregulation of Bax. Cytosolic cytochrome c increased by 43.0% with celecoxib and TNF-α treatment but was not significant with celecoxib and cisplatin treatment. Nuclear AIF increased by 21.0% with celecoxib and cisplatin treatment whereas it was not significant with celecoxib and TNF-α treatment. The mRNA level of Mn-Superoxide dismutase, CuZn-Superoxide dismutase, Glutathione peroxidase and Catalase decreased significantly on priming with celecoxib and then treating with cisplatin or TNF-α. There was no significant increase in the activity of caspase-3 with either celecoxib or TNF-α treatment or with celecoxib and cisplatin treatment. The findings suggest that priming with celecoxib induces the TNF-α and cisplatin-mediated apoptosis in SiHa cells perhaps through ROS-mediated mitochondrial pathway.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Kuhar
authors.forename: Sabiha
authors.initials: S
authors.lastname: Imran
authors.forename: Neeta
authors.initials: N
authors.lastname: Singh
keywords: TNF-α; apoptosis celecoxib; cervical cancer; cisplatin; mitochondria