Lung cancer is a major public health issue worldwide and is associated with high mortality and poor prognosis.
Chemotherapy has the potential to reduce
tumor size, increase operability and eradicate
micrometastases; therefore, novel chemicals to treat
lung cancer are urgently required. In the present study, the effects of N, N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4, 5-tetrazine-1,4-dicarboamide (ZGDHu-1), a novel tetrazine derivative, were investigated in A549 and RERF-LC-MA
lung cancer cells, and the underlying molecular mechanism of ZGDHu in treating
lung cancer was determined. Following incubation with different concentrations of
ZGDHu-1, flow cytometry analysis results indicated that
ZGDHu-1 could induce G2/mitotic (M) cell cycle arrest and apoptosis in A549 and RERF-LC-MA cells in a dose-dependent manner. Furthermore, western blot analysis demonstrated that the expression levels of G2/M regulatory molecules, including
cyclin B1, Cdc2 and cell division cycle 25c, decreased following treatment with
ZGDHu-1, whilst p53 expression increased. In addition, A549 and RERF-LC-MA cell apoptosis was induced by cell cycle arrest at the G2/M phase and through the downregulation of nuclear factor-κB. These results suggest that
ZGDHu-1 may induce G2/M phase arrest and apoptosis of
lung cancer cells, and may serve as a potential therapeutic
drug for the treatment of
lung cancer.