Targeting Ferroptosis in Cancer by Natural Products: An Updated Review

Ferroptosis is a new cell death process characterized by massive iron accumulation and lipid peroxidation. Emerging evidence demonstrates that ferroptosis plays a crucial role in the development and progression of tumorigenesis. Targeting it is a potentially effective cancer prevention and treatment strategy in the clinic. A comprehensive review of molecular mechanisms of targeting ferroptosis in cancer by natural products needs to be re-summarized and updated due to the advances in research. We searched and reviewed relevant literature through the database Web of Science, mainly focusing on the regulatory effects of natural products and their active compounds in treating or preventing cancer by regulating ferroptosis. A total of 62 kinds of natural products and their active compounds were reported to exert antitumor effects via causing ferroptosis of cancer cells by regulating the System Xc(-)-GPX4 axis and lipid, mitochondrial, and iron metabolism. Natural products have advantages in improving chemotherapy's therapeutic effects by causing cancer cell ferroptosis through their polypharmacological actions. These molecular mechanisms of ferroptosis regulation by natural products will pave the way for developing natural antitumor drugs based on regulating ferroptosis.