The Effects And Mechanisms Of Emodin Derivative WJL-19 In Burkitt Lymphoma Cell Lines CA46 And Raji

Objective : To explore the effect of WJL-19,a novel emodin derivative,on the proliferation,apoptosis,mitochondrial membrane potential,intracellular ROS level,cytochrome c and apoptosis related protein of Burkitt lymphoma cell lines CA46 and Raji,to investigate the possible mechanism of WJL-19 induced apoptosis in BL cells,and to provide experimental evidence for the future application of WJL-19 in clinic.Methods : Selecting the Burkitt lymphoma cell lines CA46 and Raji as the experimental objects,which was cultured with different concentrations of WJL-19 at different times,then MTT test and clone formation experiment were used to measure cell proliferation.Annexin V-PE/7-AAD double staining and DAPI staining were used to study the effect of WJL-19 on apoptosis of CA46 and Raji.JC-1 and DCFDA combined with flow cytometry were used to detect the changes of mitochondrial membrane potential and the levels of ROS after drug treatment.Caspase 3,caspase9,PARP,c-myc,Bcl-2,Bax,survivin proteins as well as Cyt c protein in mitochondrion and cytoplasm were detected by Western blot after 24 h treatment with WJL-19.Results : 1.Emodin derivative WJL-19 can inhibit the proliferation of Burkitt lymphoma CA46 cells and Raji cells and keep a concentration effect and time effect relationship.2.The apoptosis of CA46 and Raji cells is significantly induced by WJL-19(P<0.01).3.WJL-19 can promote CA46 and Raji cells to produce a large number of ROS(P<0.01),which causes the significant changes of mitochondrial membrane potential in CA46 and Raji cells(P<0.01).4.WJL-19 can promote the release of Cyt c from mitochondrion in Burkitt lymphoma CA46 cells and Raji cells.5.With the increase of drug concentration after WJL-19 treatment for 24 h,the Proapoptotic proteins' expression of Bax,Caspase-3,9 and PARP were significantly increased,while the oncogene proteins' expression of Bcl-2,c-myc and survivin were significantly decreased.Conclusion:1.The new emodin derivative WJL-19 can effectively inhibit theproliferation of Burkitt lymphoma cell lines CA46 and Raji and induce the apoptosis of tumor cells.2.WJL-19 can up-regulate the level of ROS,promote the decrease of mitochondrial membrane potential,increase the release of Cyt c,induce Caspase cascade reaction.3.The possible mechanism of WJL-19 induced apoptosis in Burkitt lymphoma cells above may be due to the production of ROS and mitochondrial Signaling pathway and play the role of anti Burkitt lymphoma.