LC-MS/MS Analysis of Renal Cell Carcinoma Treated with Sulforaphane
Description
Sulforaphane(SFN)isanisothiocyanate(ITC)derivedfromcruciferousvegetables,suchasbroccoli,thatisgrowinginpopularityforitsantioxidantandanti-inflammatorycapabilities.
Furthermore,SFNhasbeendemonstratedtoimproverenalcancercarcinoma(RCC)treatment
outcomesinconjunctionwithmultipleotherformsoftherapy,whichisespeciallyimportant
consideringRCC’spoortherapeuticoutcomeswithchemotherapy.Theaimofthisstudywasto
determinetheeffectsofSFNonRCC invitro utilizingcellviabilityanalysisandLC/MS-MS
targetedmetabolicprofilingtorevealpathwaysresponsibleforSFN’spossibleenhancementof
chemotherapytreatmentinRCC.CCK-8resultsshowthat15 μMofSFNcausedasignificant(p
<0.05)increaseinRCCproliferation.Kruskal-Wallistestsrevealed16metabolitesinourcell,
and28inthemediumtobesignificant(p<0.05).Anorthogonalpartialleastsquares-discriminant
analysis,OPLS-DA,ofsignificantmetaboliteswasusedtocomparedtreatedandnon-treated
samplesforbothdatasetsandshoweda100%predictiveaccuracy(AUC=1).Enrichment
analysisdeterminedthatatotalof7metabolicpathwaysweresignificantlyenriched(VLCFA
β-oxidation,glutamatemetabolism,theureacycle,ammoniarecycling,glycine/serine,alanine,
andglucose-alaninecycle).Pathwayanalysisshowedhistidinemetabolismtobetheonly
significantlyaffectedpathwaybetweenbothdatasets.SFN-inducedmetaboliccharacteristics
foundinRCCwereconsistentwithknownantioxidantandanti-inflammatorypathways.Ourdata
suggeststhatthetherapeuticmechanismsofSFNarelikelyduetointeractionswithTandNKT
cellsthatprotectthemfromoxidativestress.Futureexperimentsregardingantioxidantresearch
incancershouldbecompletely invivo,asopposedto invitro, inordertomaintainthenatural
physiology of cancer cells in the presence of host immune cells.
Date Created
The date the item was original created (prior to any relationship with the ASU Digital Repositories.)
2019-05
Agent
- Co-author: Hrovat, Jonathan Matthew
- Co-author: Bresette, William
- Thesis director: Gu, Haiwei
- Committee member: Jasbi, Paniz
- Contributor (ctb): School of Life Sciences
- Contributor (ctb): Barrett, The Honors College