Paeonol Inhibits Cell Growth by Inducing Ferroptosis in Human Glioma Cells

Paeonol (PAE), a phenolic phytochemical derived from traditional Chinese medicinal plants, exhibits multifaceted pharmacological properties including demonstrated antitumor efficacy against hepatic, gastric, and breast carcinomas. However, its therapeutic potential in glioma remains unexplored. Ferroptosis, a regulatory cell death pathway dependent on iron content mediated through lethal lipid peroxidation, has become a prospective method for targeted treatment of drug-resistant malignant tumors. This study confirmed that PAE is a new inducer of ferroptosis in human glioma cells. Inhibition of glioma proliferation, migration, and invasion was observed. Mechanistically, PAE depletes lipid droplets (LDs) and amplifies cytotoxic lipid peroxides (LPO) and reactive oxygen species (ROS); caspase-independent cell death was achieved. Crucially, ferroptosis inhibitors (ferrostatin-1, α-tocopherol) reversed PAE's antineoplastic roles, confirming pathway specificity. These findings position PAE as a dual-action agent capable of simultaneously inducing ferroptosis and impeding metastatic spread, offering a mechanistically distinct approach to overcome temozolomide resistance in glioma therapeutics.