title: Indomethacin antagonizes EP(2) prostanoid receptor activation in LS174T human colon cancer cells.
abstract: Increases in the level of cyclooxygenase (COX)-2 and prostanoids such as prostaglandin E(2) (PGE(2)) are considered biomarkers of colorectal cancer. Therefore, non-steroidal anti-inflammatory drugs (NSAID) have been used to reduce the risk of cancer development by reducing prostanoid biosynthesis as COX inhibitors. Along with their activity as COX inhibitors, NSAID have been reported to have other effects. One major NSAID, indomethacin, has been shown to have several effects independent of COX inhibition. To further examine the COX-inhibition-independent effects of indomethacin on colorectal cancer, we used human colon cancer LS174T cells, known to have express little COX-2 and have no detectable PGE(2) production. Here we show that indomethacin has a potential antagonizing effect on human EP(2) receptors. We believe this study raises the reasons to use indomethacin as a lead-compound for setting up another EP(2) receptor-specific antagonist as a relatively cost-efficient strategy for anti-cancer medication in the future.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ikawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Fujino
authors.forename: Sho
authors.initials: S
authors.lastname: Otake
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D012633:Secretin / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; C545644:PTGER2 protein, human; D011453:Prostaglandins; D058307:Receptors, Prostaglandin E, EP2 Subtype; D012633:Secretin; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; D007213:Indomethacin