Methyl Jasmonate Induces Apoptosis And Pro-apoptotic Autophagy Via The ROS Pathway In Human Non-small Cell Lung Cancer

Methyl jasmonate (MJ), a fatty acid belongs to the jasmonate family derived cyclo pentanes, is a plant stress hormone, which can act as signal transduction intermediates and regulate cell death in stressed plants. Recently, MJ was reported to have selective cytotoxic effects against drug-resistant cancer cells. MJ has diverse impacts on cancer cells including arresting cell cycle, in-hibiting Warburg Effect, inducing apoptosis and non-apoptotic cell death. However, the mecha-nism underlying MJ-induced apoptosis remains largely uncharacterized. In this study, we exam-ined the molecular mechanism of apoptosis induced by MJ in human lung cancer. We demon-strated that MJ triggered apoptosis via inducing the DDIT3-TNFRSF10B-CASP axis in human NSCLC cells. Furthermore, we showed decreased expression of CFLAR, an inhibitor of CASP8 after MJ treatment and that enforced expression of CFLAR partly protected cells from apoptosis. Moreover, we found that MJ also induced autophagy and the triggered autophagy played a pro-apoptotic role in human NSCLC cells, resulting in enhanced apoptotic cascade. At last, we found inhibition of ROS accumulation could decline both MJ-induced apoptosis and autophagy. Taken together, our findings show the underpinnings of MJ-induced apoptosis, provide evidence that MJ treatment will be an effective strategy for cancer therapy and suggest that combination treat-ment of MJ and autophagy accelerants may have synergetic effect to target cancer cells.