Description
Difluoromethylornithine(DFMO)exhibitsanti-parasitic,anti-angiogenic,anti-metastatic,anticancerchemotherapeutic,andchemopreventiveactivities.DFMOinhibitsornithinedecarboxylase,suppressingpolyamineandthymidinesynthesis.DFMOinhibitsgrowthofLeishmaniaandTrypanosomaandisclinicallyusedtotreatAfricansleepingsickness.ThiscompoundsuppressesbreastcancercellinvasionbyincreasingPKAsignalingandinhibitsneovascularizationinanimalmodels.Inotheranimalmodels,DFMOdecreasestheepithelial-to-mesenchymaltransition(EMT),suppressingsquamouscellcarcinomatumorgrowth;italsolimitsthedevelopmentofesophagealtumorsinvivo.
References
SinghAK,RobertsS,UllmanB,etal.Aquantitativeproteomicscreentoidentifypotentialdrugresistancemechanisminα-difluoromethylornithine(DFMO)resistantLeishmaniadonovani.JProteomics.2014May6;102:44-59.PMID:24631822.
TysoeC,WithersSG.Fluorinatedmechanism-basedinhibitors:commonthemesandrecentdevelopments.CurrTopMedChem.2014;14(7):865-74.PMID:24484426.
ArumugamA,WengZ,TalwelkarSS,etal.Inhibitingcycloxygenaseandornithinedecarboxylasebydiclofenacandalpha-difluoromethylornithineblockscutaneousSCCsbytargetingAkt-ERKaxis.PLoSOne.2013Nov8;8(11):e80076.PMID:24260338.
XuH,WashingtonS,VerderameMF,etal.ActivationofproteinkinaseA(PKA)signalingmitigatestheantiproliferativeandantiinvasiveeffectsofalpha-difluoromethylornithineinbreastcancercells.BreastCancerResTreat.2008Jan;107(1):63-70.PMID:17333334.
LimaeSilvaR,SaishinY,SaishinY,etal.Suppressionandregressionofchoroidalneovascularizationbypolyamineanalogues.InvestOphthalmolVisSci.2005Sep;46(9):3323-30.PMID:16123436.
FongLY,NguyenVT,PeggAE,etal.Alpha-difluoromethylornithineinductionofapoptosis:amechanismwhichreversespre-establishedcellproliferationandcancerinitiationinesophagealcarcinogenesisinzinc-deficientrats.CancerEpidemiolBioMarkersPrev.2001Mar;10(3):191-9.PMID:11303587.
