title: Indomethacin, a cox inhibitor, enhances 15-PGDH and decreases human tumoral C cells proliferation.
abstract: High levels of prostaglandins (PGs) are currently found in tumoral cells, due to expression of the inducible PGs synthesis enzyme, the cyclooxygenase 2 (COX 2). Non Steroidal Anti Inflammatory Drugs (NSAIDs) possess an antitumoral effect related, in a large extend, to the inhibition of this enzyme. It was recently suggested that the decreased activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme catabolysing PGs, may be responsible too for experimentally induced colon tumor enhancement. We report here, for the first time, that indomethacin, an NSAID, decreased TT cell proliferation, derived from a human Medullary Thyroid Carcinoma (MTC). This effect is time and concentration-dependent. Moreover, indomethacin enhanced expression and activity of 15-PGDH. The 15-PGDH levels were negatively correlated with TT cell proliferation (r = -0.52, p < 0.001). Indomethacin, known to decrease COX levels and activity, could also act in modifying catabolism of PGs. This suggests that 15-PGDH is involved in tumoral development, and could therefore be considered as a target for NSAIDs.
authors.affiliation: INSERM U 349, H pital Lariboisière, Centre Viggo Petersen, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Frenkian
authors.forename: N
authors.initials: N
authors.lastname: Segond
authors.forename: E
authors.initials: E
authors.lastname: Pidoux
authors.forename: R
authors.initials: R
authors.lastname: Cohen
authors.forename: A
authors.initials: A
authors.lastname: Jullienne
mesh_terms: D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000473:pathology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D007213:Indomethacin