title: Dual function of nonsteroidal anti-inflammatory drugs (NSAIDs): inhibition of cyclooxygenase and induction of NSAID-activated gene.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used drugs for the treatment of inflammatory disease and have a chemopreventive effect on colorectal cancer. NSAIDs inhibit cyclooxygenase (COX)-1 and/or COX-2 activity, but the chemopreventive effect may be, in part, independent of prostaglandin inhibition. NSAID-activated gene (NAG-1) was previously identified as a gene induced by some NSAIDs in cells devoid of COX activity. NAG-1 has proapoptotic and antitumorigenic activity in vitro and in vivo. To determine whether the induction of NAG-1 by NSAIDs is influenced by COX expression, we developed COX-1- and COX-2-overexpressing HCT-116 cells. COX expression did not affect NSAID-induced NAG-1 expression as assessed by transient and stable transfection. Also, NAG-1 expression was not affected by PGE(2) and arachidonic acid, suggesting that NAG-1 induction by NSAIDs occurs by a prostanoid-independent manner. We also report that indomethacin increased NAG-1 expression in a number of cells from tissues other than colorectal. In conclusion, NSAIDs have dual function, induction of NAG-1 expression and inhibition of COX activity that occurs in a variety of cell lines.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Wilson
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Eling
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D015232:Dinoprostone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D055436:Growth Differentiation Factor 15; D006801:Humans; D007213:Indomethacin; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin