SIRT3 has been found to involve in the tumorigenesis and progression of glioblastoma, and it is reported that puerarin can inhibit the growth of glioblastoma cells. Therefore, we aimed to investigate the biological function of SIRT3 in autophagy and ferroptosis in glioblastoma cells and study the effects of puerarin on ferroptosis and SIRT3/NCOA4-dependent autophagy in cancer cells. The results showed that overexpression of SIRT3 significantly promoted ferroptosis sensitization by reducing cell viability and GSH/GSSH ratio and increasing ROS levels, whereas knockout of SIRT3 significantly triggered cell viability and GSH/GSSH ratio and decreasing ROS levels in U87MG cells (P <
0.05). Moreover, overexpression of SIRT3 significantly also promoted the ratio of LC3-Ⅱ/Ⅰ and upregulated NCOA4 and Fe