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

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 G(2)/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 p21(WAF1/CIP1) and p27(KIP1), 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 p21(WAF1), 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 G(2)/M phase and apoptosis in A549 and H460 cells, which was likely mediated via the p53/p21(WAF1/CIP1) and p27(KIP1) pathways. Overall, the results indicated that JS-K may be used as an anticancer agent for the treatment of NSCLC.