Open AccessInduction of G2/M phase arrest and apoptosis by ZGDHU-1 in A549 and RERF-LC-MA lung cancer cells
Author(s) -
Xinfeng Shen,
Zhiyong Wu,
Sufeng Chen,
Yu Chen,
Jun Xia,
Yaping Lv,
Yonglie Zhou
Publication year - 2016
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2016.4697
Subject(s) - cell cycle , lung cancer , cancer research , a549 cell , biology , apoptosis , cell cycle checkpoint , oncology , medicine , biochemistry
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 G 2 /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 G 2 /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 G 2 /M phase and through the downregulation of nuclear factor-κB. These results suggest that ZGDHu-1 may induce G 2 /M phase arrest and apoptosis of lung cancer cells, and may serve as a potential therapeutic drug for the treatment of lung cancer.