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.