Dioscin Promotes Ferroptosis in Cervical Cancer Cells via the TIGAR-ROS Axis

Cervical cancer seriously threatens women's life and health, highlighting the urgent need for targeted therapies. TP53-induced glycolysis regulatory phosphatase (TIGAR), upregulated in cervical cancer and regulated by HPV E6, may be involved in cervical cancer progression, making its inhibition a potential therapeutic strategy. This study aims to investigate the role and mechanism of TIGAR in cervical cancer ferroptosis resistance and identify a TIGAR-targeting drug to suppress cervical cancer advancement. Through RNA-seq, transmission electron microscopy, and western blotting, we found that TIGAR knockdown significantly promoted ferroptosis by increasing intracellular lipid reactive oxygen species (ROS) levels. Furthermore, through molecular docking, CETSA, and SPR analysis, we identified Dioscin as a compound that binds to TIGAR. Dioscin treatment effectively inhibited cervical tumors via TIGAR both in vitro and in vivo. Mechanistically, Dioscin interacted with TIGAR and promoted ferroptosis, at least in part, through the TIGAR-ROS axis. Collectively, these findings indicate that TIGAR suppresses ferroptosis via lipid ROS reduction, while Dioscin counteracts this process, at least in part, through the TIGAR-ROS axis. Thus, Dioscin holds promise as a potential targeted therapeutic agent for cervical cancer.