title: Induction of G2/M phase arrest and apoptosis by ZGDHU-1 in A549 and RERF-LC-MA lung cancer cells.
abstract: 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.
authors.affiliation: Inspection Department, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China; Clinical Laboratory Center, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Shen
authors.affiliation: Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Clinical Laboratory Center, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Sufeng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Inspection Department, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Clinical Laboratory Center, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Laboratory Center, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Clinical Laboratory Center, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yonglie
authors.initials: Y
authors.lastname: Zhou
keywords: A549; RERF-LC-MA; ZGDHu-1; apoptosis; cell cycle