The emergence of multidrug resistance (MDR), meaning that cancer cells develop simultaneous resistance to different drugs, has limited the clinical efficacy and application of chemotherapy. Pterostilbene, a naturally occurring phytoalexin exerts a variety of pharmacologic activities, including antioxidation, cancer prevention and cytotoxicity to various cancer cells. In this study, results approved the capability of pterostilbene to effectively inhibit the cell growth of docetaxel-induced multidrug resistance human lung cancer cells lines and such inhibition is through an induction of cell cycle arrest and apoptosis. Meanwhile, the observation of the formation of acidic vesicular organelles and LC3-II production revealed an induction of autophagy at an early stage by pterostilbene, which was triggered by an inhibition of the AKT and JNK and an activation of the ERK1/2 pathway. Furthermore, an inhibition of autophagy by pretreatment with 3-methyladenine, bafilomycin A1 or Beclin 1 siRNA was able to enhance pterostilbene-triggered apoptosis. In conclusion, this study demonstrate that pterostilbene causes autophagy and apoptosis in lung cancer cells. Furthermore, a combination of pterostilbene with autophagy inhibitors may strengthen the efficiency of proapoptotic chemotherapeutic strategies in both chemosensitive and chemoresistant lung cancer cells, which may be of great value for the clinical management of lung cancer patients with multidrug resistance.
