Lupeol triterpene exhibits potent antitumor effects in A427 human lung carcinoma cells via mitochondrial mediated apoptosis, ROS generation, loss of mitochondrial membrane potential and downregulation of m-TOR/PI3K/AKT signalling pathway

Purpose: Lung cancer is one among the most commonly diagnosed malignancies in developed countries with highest rates of morbidity and mortality. The treatment options for lung cancer are limited and have side effects. Hence, researches are being directed at the exploration and evaluation of new molecules showing anticancer activity. In this study we investigated the anticancer effects of lupeol on the lung cancer A427 cancer cells and normal MRC-5 cells. Methods: Growth inhibitory effects were checked by MTT assay. Apoptosis was detected by DAPI and annexin V/PI staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were estimated by flow cytometry. Protein expression analysis was performed by western blotting. Results: The results showed that lupeol inhibited the growth of A427 lung cancer cells as observed by MTT and colony formation assay. The antiproliferative effects were due to induction of apoptosis as indicated by DAPI and annexin V/PI staining. This was further confirmed by Bax and Bcl-2 expression. Moreover, lupeol triggered generation of ROS and decrease of MMP. Lupeol could also inhibit the mTOR/PI3K/AKT signalling pathway. Taken together, lupeol could prove beneficial in the treatment of lung cancer. Conclusions: In brief, the present study indicated that lupeol induced potent and selective cytotoxic effects and these effects were mediated via apoptosis, ROS generation, loss of MMP and inhibition of mTOR/PI3K/AKT signalling pathway.