title: ZGDHu-1 promotes apoptosis of chronic lymphocytic leukemia cells.
abstract: Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable             with conventional modalities of chemotherapy. We aimed to examine the proapoptotic             effects of a novel proteasome inhibitor, N,N'-di-(m-methylphenyi)-3,6- dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1),             on CLL cells. B lymphocytes were isolated from CLL patients and normal healthy             controls, and treated with various concentrations of ZGDHu-1 for different days.             CLL cell viability was detected by MTT assay. The apoptosis, mitochondrial membrane             potential (∆ψm) and reactive oxidative species (ROS) were examined by flow cytometry.             The expression of caspase-3 and Bcl-2/Bax ratio was detected by western blotting.             ZGDHu-1 significantly reduced the viability of CLL cells and induced apoptosis             in comparison to the control cells (both P<0.05). Normal peripheral B cells             were resistant to the apoptosis-inducing effects of ZGDHu-1. Apoptosis induced             by ZGDHu-1 was accompanied with generation of ROS, loss of ∆ψm, downregulation             of Bcl-2 and increase of caspase-3 cleavage. Results of this study indicate that             ZGDHu-1 is a promising specific treatment for CLL in the clinic.
authors.affiliation: Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China. qlv2012@126.com
authors.forename: Lian-Nv
authors.initials: LN
authors.lastname: Qiu
authors.forename: Yong-Lie
authors.initials: YL
authors.lastname: Zhou
authors.forename: Zhen-Ni
authors.initials: ZN
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Wei-Xiao
authors.initials: WX
authors.lastname: Hu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D051336:Mitochondrial Membranes / Q000378:metabolism; D010539:Permeability; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D006573:Heterocyclic Compounds, 1-Ring; C522668:N,N-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboxamide; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3