The Study On Epigenetic Alteration In Leukemia Regulated By Quercetin

Objective:Leukemia is a malignant disease originated from hematopoietic system,the epidemiologicalinvestigation showed that the incidence of leukemia in5-6/10000,and located in the sixth placein the malignant tumors and new patients each year4-5million people.The leukeogenesis anddevelopment have been confirmed with multiple cytogenetics abnormalities. Presently, leukemiais still difficult to treat. A large number of researches documented that epigenetic modification isclosely related to leukeogenesis.Numerous studies show that there is an intensive relationshipbetween the disequilibrium of epligetics and the occurance of leukemia.Here we investigated theeffects of quercetin on cell proliferation,cell cycle arrest,apoptosis,histone H3and H4acetylation,histone H3K9and H3K27trimethylation,and exprssion of the corresponding histonedeacetylase and histone methyltransferass in vitro,tring to explore the anti-leukemia mechanism.Methods:The effect of quercetin on the growth of NB4cell was studied by CCK-8assay andcompared with PBMC.Effects of quercetin on the cell cycle distribution of NB4cells werestudied by propidium iodide method.Apoptosis was detected by Hoechst3325and AnnexinV-FITC/PI double-labeled cytoetry and caspase-3and caspase-9activities were measured byspectrophotometry.The protein expression of acetyl-histone H3and H4,histone H3K9me3,H3K27me3,HDAC8,SUV39H1and EZH2were detemined by Western blot.The mRNAexpression of HDAC8was assessed by RT-PCR,while the mRNA expression of SUV39H1andEZH2were by Real-time RT-PCR.Confocalmicroscopy was used to evaluate the subcellulrdisposition and expression of HDAC8, SUV39H1and EZH2.Results:Quercetin inhibited the proliferation of NB4cells dose-and time-dependently,quercetincaused G0/G1arrest and induced apoptosis in a time-and dose-dependent maner.quercetinremarkably increased the acetylation of histone H3and H4by decreasing the expression ofHDAC8while delined histone H3K9me3and H3K27me3via inhibiting the expression ofSUV39H1and EZH2respectively.Conclusion:Quercetin can inhibit cell proliferation,cause G0/G1arrest and induce caspase dependent- apoptosis of NB4cells signifeicantly.quercetin increased the acetylation of histone H3and H4by decreasing the expression of HDAC8while declined histone H3K9me3and H3K27me3viainhibiting the expression of SUV39H1and EZH2respectively,which is possibly theanti-leukemia mechanism of quercetin.