Oxymatrine\nInhibits Liver Cancer Progression by Regulating\nSIRT1/YY1/GPX4 Axis-Mediated Ferroptosis

Ferroptosis is regarded as a promising cancer therapeutic\ntarget.\nAs a major bioactive compound from traditional Chinese medicine (TCM)\nherb Sophora flavescens Aiton, oxymatrine\n(OMT) can depress inflammatory factors, reduce iron deposition, and\nsuppress the hub gene or protein expression involved in ferroptosis\nand inflammation. Additionally, OMT can control collagen deposition\nin the liver and has a therapeutic effect on liver cancer. This research\ninvestigated the action mechanism of the mechanism of the effect of\nOMT on the process of liver cancer. OMT triggered cell death and restrained\ncell proliferation in liver cancer cells, along with downregulated\nlevels of Yin Yang 1 (YY1) and glutathione peroxidase 4 (GPX4) and\nelevated expression of silent information regulator 1 (SIRT1). Moreover,\nferroptosis is the main method leading to OMT-induced liver cancer\ncell death. OMT-induced ferroptosis was reversed after GPX4 and YY1\noverexpression or inhibition of SIRT1. Furthermore, the OMT restrained\ntumor growth through the SIRT1/YY1/GPX4 axis in liver cancer transplantation\nmodels. These results indicated that OMT inhibited cell viability\nand induced ferroptosis of liver cancer cells, involving the regulatory\nmechanism of the SIRT1/YY1/GPX4 axis.