Carotenoids as ferroptosis modulators: molecular mechanisms and implications for food and health.

Carotenoids, a class of natural fat-soluble pigments widely distributed in fruits and vegetables, are known for their diverse bioactivities, including antioxidant and anti-inflammatory effects. Notably, oxidative stress and lipid peroxidation are central processes in ferroptosis and key targets of carotenoid activity. Ferroptosis is a recently identified form of regulated cell death featuring iron-dependent lipid peroxidation, mechanistically distinct from other types of cell death. In recent years, growing evidence has revealed that carotenoids can modulate ferroptosis through multiple pathways, thereby influencing disease progression. Current investigations suggest that certain carotenoids may play a context-dependent dual role in regulating ferroptosis. In non-malignant cells/tissues exposed to toxins or pathological stress, they inhibit ferroptosis and confer cytoprotection. In contrast, in cancer cells, carotenoids can promote ferroptosis and thereby suppress tumor growth. In this review, we summarize recent advances in how carotenoids modulate ferroptosis, emphasizing the underlying molecular mechanisms and discussing their potential applications in cancer prevention, protection against toxin-induced injury, and the treatment of ferroptosis-related conditions such as neurodegenerative disorders, cardiovascular diseases, and inflammatory diseases.