Menthol induces apoptosis and inhibits proliferation and migration of nonsmall cell lung carcinoma in vitro and in vivo through Akt pathway.

Abstract

About 40% of nonsmall cell lung cancers (NSCLCs) have already progressed in an advanced stage at the time of diagnosis. Development of effective prevention and therapy approaches against NSCLC is critical for reducing mortality. As a fundamental ingredient of peppermint oil, menthol has been demonstrated to possess an antitumor activity in several types of carcinomas. However, the potential role of menthol on NSCLC has not been reported. The present study aims to investigate the effect and underlying mechanism of menthol on proliferation, apoptosis, and mobility of human lung adenocarcinoma. Cell apoptosis was examined by MTT and flow cytometry. The motility of cells was determined by Transwell assay. Western blot analysis was performed to determine expression level of proteins. In vivo model of nude mice was established for evaluating the influence of menthol on tumorigenicity of A549 cells. The expression lentiviral vector of Akt was established in NSCLC cells for further verifying the inhibiting effect of menthol on survival and mobility of NSCLC cells via Akt pathway. The results showed that menthol promoted A549 cell apoptosis, suppressed cell proliferation, and motility by altering the phosphorylated protein level of Akt. Menthol enhanced the expression level of Bax while decreasing expression of Bcl-2, Caspase-3, and MMPs proteins. In vivo experiments suggested that menthol exhibited an inhibitory effect in tumor growth on xenografts. These results were further validated in Akt over-expressed A549 and H1299 cells. Menthol could display an inhibitory effect on NSCLC cells through Akt signaling pathway, making it a potential target for NSCLC treatment.