Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition 英文参考文献.docVIP

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Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition 英文参考文献.doc

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Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition 英文参考文献

GreenTeaCatechinsReduceInvasivePotentialofHuman MelanomaCellsbyTargetingCOX-2,PGE2Receptorsand Epithelial-to-MesenchymalTransition TriptiSingh1,SantoshK.Katiyar1,2,3,4* 1DepartmentofDermatology,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica,2NutritionObesityResearchCenter,Universityof AlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica,3ComprehensiveCancerCenter,UniversityofAlabamaatBirmingham,Birmingham,Alabama, UnitedStatesofAmerica,4BirminghamVeteransAffairsMedicalCenter,Birmingham,Alabama,UnitedStatesofAmerica Abstract Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastaticability.Todevelopmoreeffectivechemopreventiveagentsforthepreventionofmelanoma,wehavedetermined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model.Employingcellinvasionassays,wefoundthattheinhibitoryeffectsofgreenteacatechinsonthecellmigrationwere in the order of (-)-epigallocatechin-3-gallate (EGCG).(-)-epigallocatechin.(-)-epicatechin-3-gallate.(-)-gallocatechin.(-)- epicatechin.TreatmentofA375andHs294tcellswithEGCGresultedinadose-dependentinhibitionofcellmigrationor invasionofthesecells,whichwasassociatedwithareductioninthelevelsofcyclooxygenase(COX)-2,prostaglandin(PG)E2 and PGE2 receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration.EGCGinhibits12-O-tetradecanoylphorbol-13-acetate-,aninducerofCOX-2,andPGE2-inducedcellmigrationof cells.EGCGdecreasedEP2agonist(butaprost)-andEP4agonist(Cay10580)-inducedcellmigrationability.Moreover,EGCG inhibitedtheactivationofNF-kB/p65,anupstreamregulatorofCOX-2,inA375melanomacells,andtreatmentofcellswith caffeicacidphenethylester,aninhibitorofNF-kB,alsoinhibitedcellmigration.Inhibitionofmelanomacellmigrationby