Anticancer mechanism of plumbagin, a natural compound, on non-small cell lung cancer cells.

Abstract

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the United States. Prevailing treatment options have limited therapeutic success in lung cancer, particularly non-small cell lung cancer (NSCLC), as it becomes resistant to therapy. Hence, better therapeutic options are immediately required for lung cancer. Plumbagin, a natural compound has been recently examined for its anticancer effect on different cancers. MATERIALS AND METHODS: To determine the anticancer effect of plumbagin on NSCLC cell lines H460 and A549, cell viability, apoptotic, Western blot and reporter assays were performed. RESULTS: Plumbagin significantly inhibited the growth of H460 cells compared to A549 cells, and down-regulated the expression of EGFR/Neu and its downstream signaling (Akt, NF-kappaB, Bcl-2 and survivin) in H460 cells. In addition, plumbagin up-regulated the expression of p53 and p21(CIP1/WAF1) causing cell cycle arrest in the G2/M-phase by down-regulating G2/M regulatory proteins (cyclinB1 and Cdc25B) in H460 cells. Furthermore, it activated the JNK/p38 signaling, leading to caspase-3 activation resulting in the induction of apoptosis. CONCLUSION: Plumbagin exerted anticancer activity on NSCLC cells by modulating the pro-survival and pro-apoptotic signaling that causes induction of apoptosis.