Induction of G2/M phase arrest and apoptosis by ZGDHU-1 in A549 and RERF-LC-MA lung cancer cells

Shen,Xinfeng; Wu,Zhen; Chen,Sufeng; Chen,Yu; Xia,Jun; Lv,Yaping; Zhou,Yonglie

doi:10.3892/ol.2016.4697

Induction of G2/M phase arrest and apoptosis by ZGDHU-1 in A549 and RERF-LC-MA lung cancer cells

Authors:
- Xinfeng Shen
- Zhen Wu
- Sufeng Chen
- Yu Chen
- Jun Xia
- Yaping Lv
- Yonglie Zhou
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Affiliations: Inspection Department, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China, Clinical Laboratory Center, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Laboratory Center, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P.R. China
Published online on: June 9, 2016 https://doi.org/10.3892/ol.2016.4697
Pages: 989-994

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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.

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