ZGDHu-1 for cancer therapy (Review)

Abstract

N,N’-di-(m-methylphenyl)-3,6-dimethyl-1,4- dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) is a novel tetrazine derivative that was initially designed and produced by Professor W.X. Hu, and which has been reported by our group to exhibit antitumor activity. Accumulating evidence suggests that the anticancer mecha- nisms of ZGDHu-1 may be involved indifferent biological activities, particularly in acute myeloid leukemia (AML) cells. At a high concentration, ZGDHu-1 has been demon- strated to inhibit the proliferation of the leukemia cells by arresting the cell cycle at the G2/M phase, and by inducing cell apoptosis via inducing the accumulation of reactive oxygen species, the translocation of phosphatidylserine across the plasma membrane and the loss of mitochondrial membrane potential. Furthermore, at a low concentration, it was demonstrated to induce the differentiation and degrade the AML1-eight-twenty-one fusion protein in AML cells. Finally, results from a previous study indicate that ZGDHu-1 is a potential proteasome inhibitor. Overall, our prelimi- nary research suggests that ZGDHu-1 may be a promising anticancer drug; however, further research is warranted to identify the exact drug target and potential clinical applica- tion in leukemia cells or solid tumors. In the present review, the application of ZGDHu-1 in cancer research, in addition to the specific underlying targets of ZGDHu-1, are discussed.