JS‑K induces G2/M phase cell cycle arrest and apoptosis in A549 and H460 cells via the p53/p21WAF1/CIP1 and p27KIP1 pathways

Song,Zeqing; Yin,Yongxin; Hao,Siyuan; Wei,Jianmao; Liu,Bin; Huang,Xiaojie; Gao,Chenfeng; Zhu,Runzhi; Liao,Weiguo; Cai,De

doi:10.3892/or.2019.7104

JS‑K induces G2/M phase cell cycle arrest and apoptosis in A549 and H460 cells via the p53/p21WAF1/CIP1 and p27KIP1 pathways

Authors:
- Zeqing Song
- Yongxin Yin
- Siyuan Hao
- Jianmao Wei
- Bin Liu
- Xiaojie Huang
- Chenfeng Gao
- Runzhi Zhu
- Weiguo Liao
- De Cai
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Affiliations: Department of Respiratory Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, Guangdong 518110, P.R. China, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
Published online on: April 9, 2019 https://doi.org/10.3892/or.2019.7104
Pages: 3475-3487

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Abstract

Lung cancer is one of the most common malignancies worldwide, with high mortality and morbidity rates. O2‑(2,4‑dinitrophenyl)‑1‑[(4‑ethoxycarbonyl)piperazin‑1‑yl]diazen‑1‑ium‑1,2‑diolate (JS‑K) is a potent anticancer agent that acts against a subset of human non‑small cell lung cancer (NSCLC) cell lines; however, the underlying mechanisms of JS‑K in NSCLC remain unclear. The present study aimed to evaluate the anticancer effect of JS‑K and investigate its underlying mechanisms in A549 and H460 cells. In the present study, A549 and H460 cells were treated with JS‑K, and then evaluated by cell viability assay, flow cytometry and western blot analysis. JS‑K markedly induced cell cycle arrest at the G2/M phase in a concentration and time‑dependent manner in both cell lines. This was associated with increased expression levels of p53, and the cell cycle inhibitors p21WAF1/CIP1 and p27KIP1, which, in turn, inhibited the expression of Cdc2, cyclin B1 and cyclin‑dependent kinase 2. In addition, JS‑K‑induced inhibition of proliferation was revealed to be partially modulated by the upregulation of p53 and p21WAF1, the ratio of Bax/Bcl‑2, and the activation of both the intrinsic and extrinsic apoptotic pathways in A549 and H460 cells. These results demonstrated that JS‑K could trigger cell cycle arrest at the G2/M phase and apoptosis in A549 and H460 cells, which was likely mediated via the p53/p21WAF1/CIP1 and p27KIP1 pathways. Overall, the results indicated that JS‑K may be used as an anticancer agent for the treatment of NSCLC.

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