title: ZGDHu-1 promotes apoptosis of mantle cell lymphoma cells.
abstract: Mantle cell lymphoma (MCL) is a well-defined aggressive Non-Hodgkin-lymphoma with short survival rates and remains incurable to date. Previously, we demonstrated the antitumor activity of ZGDHu-1(N, N'-di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide) in chronic lymphocytic leukemia. In this study, ZGDHu-1 shows potent anti-lymphoma activity in MCL cells. ZGDHu-1 significantly induces cell cycle G2/M phase arrest and apoptosis in MCL cells. ZGDHu-1 reduces the protein levels of Mcl-1, Bcl-XL and cyclin D1. Importantly, ZGDHu-1 inhibits TNFα-induced IkBa phosphorylation, p65 nuclear translocation and NF-kB downstream target gene expression in MCL cells. MCL samples expressing high levels of Bcl-2 and high Bcl-2/Bax ratios tend to be less effective to ZGDHu-1. Together, these results suggest that ZGDHu-1 could inhibit the NF-kB signaling pathway partly, which may lead to the suppression of cell proliferation and the induction of apoptosis in MCL cells. Thus, our studies provide evidence of the potential of ZGDHu-1 in treating mantle cell lymphoma.
authors.affiliation: Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
authors.forename: Liannv
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Hematology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
authors.forename: Yonglie
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology*; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors
chemical_list: 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; D016328:NF-kappa B
keywords: N, N’-di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide; NF-κB; apoptosis; cell cycle; mantle cell lymphoma