简介：Eatmore‘green’oreat‘fiveaday’isoneofthemostimportanthealthylifestylebehavioursinthe21century.Aimingtofightcancereffectively,morethanhalfpatientsusevitaminsorherbsconcurrentlywithconventionalanticancertreatment.Flavonoidsorpolyphenolsexistinginvegetables,fruitsandgreenteaarecommonplantpigmentswithantioxidantpropertiesandconsideredactingascancerpreventingoranti-canceragents.RecentlyitwasfoundthatsomeflavonoidsandvitaminCindietorsupplementshaveantagonisticeffectwiththeanti-cancerdrugbortezomib.Bortezomibisaspecificinhibitorforproteasomeandiscurrentlyusedfortreatmentofrelapsedandrefractorymultiplemyeloma.Despiteitssuccessfulratesintreatingmultiplemyelomaandothersolidtumors,itisunabletokillleukemiccellsintheblood.ItwasrecentlyrevealedthatsomeflavonoidsandvitaminCpresentingreenleavesandgreenteasinthebloodcanneutralizebortezomibbydirectlyinteractionbetweentwochemicals.Herewesummarizewhydietaryflavonoidsshouldbeavoidedinpatientswhotakebortezomibaschemotherapeuticdrug.

简介：Objective:ToinvestigatetheeffectsofCAL-101,particularlywhencombinedwithbortezomib(BTZ)onmantlecelllymphoma(MCL)cells,andtoexploreitsrelativemechanisms.Methods:MTTassaywasappliedtodetecttheinhibitoryeffectsofdifferentconcentrationsofCAL-101.MCLcellsweredividedintofourgroups:controlgroup,CAL-101group,BTZgroup,andCAL-101/BTZgroup.TheexpressionofPI3K-p110σ,AKT,ERK,p-AKTandp-ERKweredetectedbyWesternblot.TheapoptosisratesofCAL-101group,BTZgroup,andcombinationgroupweredetectedbyflowcytometry.Thelocationchangesofnuclearfactorkappa-B(NF-κB)of4groupswasinvestigatedbyNF-κBKitexploring.Westernblotwasappliedtodetectthelevelsofcaspase-3andthephosphorylationofAKTindifferentgroups.Results:CAL-101dose-andtime-dependentlyinducedreductioninMCLcellviability.CAL-101combinedwithBTZenhancedthereductionincellviabilityandapoptosis.WesternblotanalysisshowedthatCAL-101significantlyblockedthePI3K/AKTandERKsignalingpathwayinMCLcells.ThecombinationtherapycontributedtotheinactivationofNF-κBandAKTinMCLcelllines.However,cleavedcaspase-3wasup-regulatedaftercombinedtreatment.Conclusion:OurstudyshowedthatPI3K/p110σisanoveltherapeutictargetinMCL,andtheunderlyingmechanismcouldbetheblockingofthePI3K/AKTandERKsignalingpathways.ThesefindingsprovidedabasisforclinicalevaluationofCAL-101andarationaleforitsapplicationincombinationtherapy,particularlywithBTZ.