Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models.docVIP

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Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models.doc

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Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models

Anti-TumorEffectsofGanodermalucidum(Reishi)in InflammatoryBreastCancerinInVivoandInVitro Models IvetteJ.Suarez-Arroyo1,RaysaRosario-Acevedo1,AlexandraAguilar-Perez1,PedroL.Clemente1, LuisA.Cubano2,JuanSerrano3,RobertJ.Schneider4,MichelleM.Mart?′nez-Montemayor1* 1DepartmentofBiochemistry,UniversidadCentraldelCaribe,SchoolofMedicine,Bayamo′n,PuertoRico,UnitedStatesofAmerica,2DepartmentofAnatomyandCell Biology,UniversidadCentraldelCaribe,SchoolofMedicine,Bayamo′n,PuertoRico,UnitedStatesofAmerica,3SanPabloPathology,Bayamo′n,PuertoRico,UnitedStates ofAmerica,4NewYorkUniversityCancerInstitute,NewYork,NewYork,UnitedStatesofAmerica Abstract ThemedicinalmushroomGanodermalucidum(Reishi)wastestedasapotentialtherapeuticforInflammatoryBreastCancer (IBC)usinginvivoandinvitroIBCmodels.IBCisalethalandaggressiveformofbreastcancerthatmanifestsitselfwithouta typicaltumormass.StudiesshowthatIBCtissuebiopsiesoverexpressE-cadherinandtheeukaryoticinitiationfactor4GI (eIF4GI),twoproteinsthatarepartiallyresponsiblefortheuniquepathologicalpropertiesofthisdisease.IBCistreatedwith amultimodalapproachthatincludesnon-targetedsystemicchemotherapy,surgery,andradiation.Becauseofitsnon-toxic andselectiveanti-canceractivity,medicinalmushroomextractshavereceivedattentionfortheiruseincancertherapy.Our previousstudiesdemonstratetheseselectiveanti-cancereffectsofReishi,whereIBCcellviabilityandinvasion,aswellasthe expressionofkeyIBCmolecules,includingeIF4Giscompromised.Thus,hereinwedefinethemechanisticeffectsofReishi focusingonthephosphoinositide-3-kinase(PI3K)/AKT/mammaliantargetofrapamycin(mTOR)pathway,aregulatorofcell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTORdownstreameffectorsatearlytreatmenttimes,asweobservereducedeIF4Glevelscoupledwithincreasedlevelsof eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected withIBCcellstreatedwithReishifor13weeksshowreducedtum