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1、TheMolecularMechanismofHDACInhibitorsinAnticancerEffectsCellular&MolecularImmunologyReview285TheMolecularMechanismofHDACInhibitorsinAnticancerEffectsGaofengBiandGuoshengJiangLHDACsandHAaretwokindsofenzymeswhichcatalysedeacetylationandacetylationofhiston
2、eineukaryotes.whosedynamicbalancehasaccurateregulationforgenetranscriptionandgeneexpressionofeukaryotesatDNAleve1.Disbalanceofthemcanbringthedisorderofproliferationanddifierentiationinnormalcells.andthenleadtotheinitiationoftumor.Theiraberrantfunctionswered
3、irectlyrelatedtotheinitiationandproRressionofvarioustumors,suchaspromyelocyticleukemia,Hodgkinlymphoma,coloniccancerandgastralcancer.TheinhibitorsofHDACsareusedfortreatmentoftumor.TheycanrestraintheactivityofHDACsandblocktheinhibitionofgeneexpressioncausedb
4、ythedisorderofdeacetylation.Itsmajorbiologicaleffectslieininducingdifferentiationoftumorcells,arrestingcellcircleatG0,G1,activatingcellapoptosisgene,enhancingthesensitivityofchemicaltherapyandradioactivetherapy.SofarHDAChasbeenanimportanttargetenzymeinantic
5、ancerdruRresearch.Cellular&MolecularImmunology.2006;3(4):285-290.KeyWords:HDACinhibitor,HATs,leukemia,differentiation,apoptosisIntroductionMostofanticancerdrugshavesideeffectsonhumannormalcellswhentheywereusedtotreattumorcells,forexample,bonemarrowdepre
6、ssionandmyocardiumdamageevencanleadtodeath.AU.transretinoicacid(ATRA,wassuccessfullyusedtotreatacutepromyelocyticleukemia(APL)bywavsofinducingdifferentiationandapoptosis(1).Thensomeeffectivedifferentiationinducersweretakentotreatothertypesofleukemiaandsolid
7、tumorsbecauseofhighremissionrateandfewsideeffects(2).Histonedeacetylase(HDAC)inhibitorsareanewclassoftargetedanticanceragents,whicharepotentinducersofgrowtharrest,differentiation.and/orapoptoticeelldeathoftransformedcellsinvitroandinvivo.SeveralHDACinhibito
8、rsareinclinicaltrialsandhaveshownsignificantactivityagainstaspectrumofbothhaematologicalandsolidtumorsatdosesthatarewelltoleratedbypatients.HDACsandhistoneacetyltransferasescan,byreversibleacetylation,
