Ithasbeenfoundthatexpressionof15-lipoxygenasc-1(15-LOX-1)anditsmainproduct,13-C-hydroxyoctadecadienoicacid(13-S-HODE),aredecreasedinhumancolorectalandesophagealcancersandthatnonsteroidalanti-inflammatorydrugs(NSAIDs)cantherspeuticallyinduce15-LOC-1expressiontotriggerapoptosisinthosecancercellsindependentlyCOX-2.WefoundthataspecificCOX-2inhibitorSC-236similarlyinduceapoptosisingastriccancercells,althoughthemechanismsoftheseeffectsremaintobedefined.Inthepresentstudy,wetestedwhetherSC-236inducedapoptosisthroughup-regulationof15-LOX-1ingastriccancercells.Wefoundthat,(a)SC-236inhibitedgrowthofgastriccancercellsmainlybyapoptosisinduced;(b)SC-236induced15-LOX-1expressionandincreasedendogenous13-S-HODEproduct,insteadof15-S-HETEduringapoptosisingastriccancercellswithout15-LOX-1expressionbeforetreatmentbySC-236;(c)sc-236didn'teffectexpressionofCOX-1,COX-2,5-LOXand12-LOX;and(d)15-LOX-1inhibitionsuppressedSC-236inducedapoptosis.ThesefindingsdemonstratedthatSC-236inducedapoptosisingastriccancercellsviaup-regulationof25-LOX-1.Theyalsosupporttheconceptthatthelossoftheproapopoticroleof15-LOX-1inepithelialcancersisnotlimitedtohumancolorectalandesophagealcancers.
