Targeting ferroptosis with resveratrol: Advances in mechanistic understanding and cancer therapy applications

Cancer continues to impose a substantial global health burden, underscoring the urgent need for innovative therapeutic strategies that can overcome resistance, improve efficacy, and minimize toxicity. Resveratrol, a naturally occurring polyphenolic stilbene found predominantly in grapes and red wine, has attracted increasing attention due to its pleiotropic bioactivities, including antioxidant, anti-inflammatory, and anticancer effects. While its roles in regulating apoptosis, cell proliferation, and immune modulation are well established, emerging evidence highlights a novel mechanistic link between resveratrol and ferroptosis, a regulated, iron-dependent form of cell death driven by lipid peroxidation. This intersection positions resveratrol as a promising candidate for addressing therapy-resistant and aggressive tumors through ferroptosis induction. Mechanistically, resveratrol has been shown to modulate iron metabolism, enhance reactive oxygen species accumulation, and influence critical regulators such as GPX4, thereby sensitizing cancer cells to ferroptotic death. This review provides a comprehensive overview of the mechanistic insights, signaling pathways, and translational perspectives at the crossroads of resveratrol and ferroptosis in cancer therapy. By integrating molecular pharmacology with emerging therapeutic strategies, we highlight the potential of resveratrol-based approaches to advance precision oncology and inspire novel ferroptosis-targeted interventions.