Isothiocyanates as Ferroptosis Inducers to Promote Cancer Cell Death.

Cancer remains a leading cause of global mortality, with the therapeutic efficacy of anticancer drugs often hampered by late diagnosis and the development of chemotherapy resistance. Ferroptosis is an iron-dependent form of regulated non-apoptotic cell death driven by lipid peroxidation. It has emerged as a potential therapeutic target to overcome drug resistance in cancer. Isothiocyanates (ITCs) from cruciferous vegetables have garnered attention for their multi-target anticancer properties. In this review, we present the key mechanisms of ferroptosis and critically evaluate current evidence indicating that ITCs can induce ferroptosis through multiple, compound-specific redox- and iron-dependent mechanisms. We further discuss whether targeting ferroptosis with ITCs may represent a novel strategy to improve anticancer treatment. Overall, ITCs emerge as versatile but tightly regulated modulators of ferroptosis in cancer, whose effective therapeutic exploitation requires further in vivo and clinical studies, biomarker-guided dose optimization, and rational combination strategies with standard anticancer chemotherapy to translate their preclinical findings into therapeutic benefit.