Chemical Constituents of Rhododendron formosanum Show Pronounced Growth Inhibitory Effect on Non-Small-Cell Lung Carcinoma Cells

The aim of the present study was to investigate whether Rhododendron formosanum Hemsl. (Ericaceae), an endemic species in Taiwan, exhibits antineoplastic potential against non-small-cell lung carcinoma (NSCLC). R formosanum was successively extracted with methanol and then separated into dichloromethane (RFL-DCM), ethyl acetate (RFL-EA), n-butanol (RFL-BuOH), and water (RFL-H2O) fractions. Among these extracts, RFL-EA exhibited the most effective antineoplastic effect. This study also demonstrated that fractions 2 and 3 from the RFL-EA extract (RFL-EA-2, RFL-EA-3) possessed the strongest antineoplastic potential against NSCLC cells. The major phytochemical constituents of RFL-EA-2 and RFL-EA-3 were ursolic acid, oleanolic acid, and betulinic acid. This study indicated that ursolic acid demonstrated the most efficient antineoplastic effects on NSCLC cells. Ursolic acid inhibited growth of NSCLC cells in a dose- and time-dependent manner and stimulated apoptosis. Apoptosis was substantiated by activation of caspase-3 and -9, and a decrease in Bcl-2 and an elevation of the Bax were also observed following ursolic acid treatment. Ursolic acid activated AMP-activated protein kinase (AMPK) and then inhibited the mammalian target of rapamycin (mTOR), which controls protein synthesis and cell growth. Moreover, ursolic acid decreased the expression and/or activity of lipogenic enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) via AMPK activation. Collectively, these data provide insight into the chemical constituents and anticancer activity of R. formosanum against NSCLC cells, which are worthy of continued study.