Effect of Sulindac Sulfide on Metallohydrolases in the Human Colon Cancer Cell Line HT-29 英文参考文献.docVIP

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Effect of Sulindac Sulfide on Metallohydrolases in the Human Colon Cancer Cell Line HT-29 英文参考文献.doc

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Effect of Sulindac Sulfide on Metallohydrolases in the Human Colon Cancer Cell Line HT-29 英文参考文献

EffectofSulindacSulfideonMetallohydrolasesinthe HumanColonCancerCellLineHT-29 HectorGuillen-Ahlers1,2,JiangningTan1,FrancisJ.Castellino1,2,3,VictoriaA.Ploplis1,2,3 * 1W.M.KeckCenterforTransgeneResearch,UniversityofNotreDame,NotreDame,Indiana,UnitedStatesofAmerica,2DepartmentofChemistryandBiochemistry, UniversityofNotreDame,NotreDame,Indiana,UnitedStatesofAmerica, 3HarperCancerResearchInstitute,UniversityofNotreDame,NotreDame,Indiana,United StatesofAmerica Abstract Matrixmetalloproteinase7(MMP7),ametallohydrolaseinvolvedinthedevelopmentofseveralcancers,isdownregulatedin coloncancermousemodelfollowingsulindactreatment.Todeterminewhetherthiseffectisrelevanttothe Min/+ theApc humancondition,HT-29humancoloncancercellsweretreatedwithsulindacanditsmetabolites,andcomparedtoresults obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindactreatmentonmetallohydrolases. Citation:Guillen-AhlersH,TanJ,CastellinoFJ,PloplisVA(2011)EffectofSulindacSulfideonMetallohydrolasesintheHumanColonCancerCellLineHT-29.PLoS ONE6(10):e25725.doi:10.1371/journal.pone.0025725 Editor:MatthewBogyo,StanfordUniversity,UnitedStatesofAmerica ReceivedFebruary3,2011;AcceptedSeptember9,2011;PublishedOctober3,2011 Copyright:?2011Guillen-Ahlersetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyNation