PHGPx Overexpression Induces an Increase in COX-2 Activity in Colon Carcinoma Cells

Background: Lipid peroxidation is a constant problem that eukaryotic cells have to face. Glutathione peroxidases (GPx) are among the most effective systems that protect cells from hydroperoxide toxicity. The objective of this study was to evaluate the relationship between GPx and cyclooxygenase 2 (COX-2), implicated in cancer pathogenesis, particularly in colon cancer cells. Materials and Methods: Phospholipid hydroperoxide glutathione peroxidase (PHGPx or GPx4), which metabolizes peroxidized phospholipids, was cloned in an expression plasmid, transfected in HT29 cl.19A colon carcinoma cells and the effects of PHGPx overexpression were measured on arachidonic acid metabolism by COX-2. Metabolites were studied by HPLC and EIA; COX-2 mRNA levels were analysed using semi-quantitative PCR. Results: Prostaglandins (PGE2, PGF2·, 6 keto-PGF1·) and thromboxane (TXB2) production were increased. COX-2 mRNA levels increased in PHGPx overexpressing cells. Conclusion: Surprisingly, our data suggest that PHGPx overexpression noticeably increases COX-2 metabolism. Hydrogen peroxide and several hydroperoxy derivatives of lipids are continuously being generated in aerobic cells by chemical or enzymatic reactions, called lipid peroxidation. Lipid peroxidation is a process involving the oxidative degradation of unsaturated lipids such as arachidonic acid (AA) and leads to the formation of many biologically active metabolites. Cyclooxygenases (COX) and lipoxygenases (LOX) are major enzymes involved in the formation of hydroperoxide metabolites and give rise to eicosanoids. These eicosanoids include prostaglandins, prostacyclins, thromboxane, hydroperoxyeicosatetraenoic acids, hydroeicosatetraenoic acids