Piperlongumine Inhibits OSCC Epithelial-Mesenchymal Transition and Promotes Tumor Cell Apoptosis by Targeting TrxR1 to Activate ROS and Its Related Pathways

Piperlongumine (PL), a naturally occurring alkaloid isolated from Piper longum fruit, has been shown to selectively toxinate a variety of tumor cells. However, PL has received less attention when it comes to oral squamous cell carcinoma (OSCC), and its precise effects and mechanisms have not been completely clarified. We verified that thioredoxin reductase 1 (TrxR1) is highly expressed in OSCC cell lines and cancer tissues of OSCC patients; PL inhibited TrxR1 activity in a concentration-dependent manner; PL inhibited OSCC cells in a concentration-dependent manner, and the inhibitory effect was more pronounced in TrxR1 low-regulated expression cells; PL could cause an increase in the level of reactive oxygen specie (ROS) in OSCC cells, and the effect was more pronounced in TrxR1 low-expression OSCC cells; PL inhibited the activation of the WNT pathway to prevent the occurrence of the epithelial-mesenchymal transition (EMT) in OSCC cells; PL activated the activation of the mitochondrial apoptotic pathway to promote the occurrence of OSCC apoptosis; and both the inhibition of the WNT pathway and the activation of the mitochondrial apoptosis by PL could be reversed by the ROS scavenger GSH. In conclusion, our research shows that PL inhibits the activity of TrxR1 in OSCC cells, increasing the level of ROS, which in turn inhibits EMT and promotes apoptosis in tumor cells by blocking the WNT pathway and activating the mitochondrial apoptosis pathway.