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.


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 rising semi-quantitative PCR.


RESULTS
Prostaglandins (PGE2, PGF2alpha, 6 keto-PGF1alpha) and thromboxane (TXB2) production were increased. COX-2 mRNA levels increased in PHGPx overexpressing cells.


CONCLUSIONS
Surprisingly, our data suggest that PHGPx overexpression noticeably increases COX-2 metabolism.
Laboratoire de Biochimie Médicale et de Génétique Moléculaire, Faculté de Médecine, 2 rue du Docteur Marcland, F-87025 Limoges Cedex, France.
Guislaine
G
Barrière
Hèlene
H
Rabinovitch-Chable
Jeanne
J
Cook-Moreau
Karine
K
Faucher
Michel
M
Rigaud
Franck
F
Sturtz
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013929:Thromboxane B2 / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone