Sophaline B inhibits non-small cell lung cancer by activating NLRP3/caspase-1/GSDMD-dependent pyroptosis and PI3K/AKT/mTOR-mediated autophagy

Sophaline B (SPB), extracted from the seeds of <i>Sophora alopecuroides</i> L., is a natural bioactive compound that effectively exerts antiviral activities against the hepatitis B virus. This is the first study to demonstrate that SPB exerts anti-tumor effects on NSCLC by inducing pyroptosis and autophagy. SPB promotes NSCLC cell death by increasing the reactive oxygen species (ROS) production to induce pyroptosis <i>via</i> activating the NLRP3/Caspase-1/GSDMD signalling pathway. Meanwhile, SPB inhibits cancer cell proliferation by activating autophagy <i>via</i> blocking the PI3K/AKT/mTOR signalling pathway. Further investigation indicates that SPB inhibits NSCLC cell migration and invasion by increasing <i>E</i>-cadherin while decreasing <i>N</i>-cadherin, vimentin, and snail at the protein level. In addition, our results show that SPB inhibits cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. Our study revealed the mechanisms of SPB triggering pyroptosis and autophagy in NSCLC, thus providing evidence and information on the SPB as an anti-cancer agent in NSCLC.