Spermine is an endogenous iron chelator that inhibits ferroptosis

Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149 , 1060–1072 (2012). Article CAS PubMed PubMed Central Google Scholar Madeo, F., Eisenberg, T., Pietrocola, F. & Kroemer, G. Spermidine in health and disease. Science 359 , eaan2788 (2018). Article PubMed Google Scholar Cañeque, T. et al. Activation of lysosomal iron triggers ferroptosis in cancer. Nature 642 , 492–500 (2025). Dai, E. et al. A guideline on the molecular ecosystem regulating ferroptosis. Nat. Cell Biol. 26 , 1447–1457 (2024). Article CAS PubMed PubMed Central Google Scholar Chen, F., Kang, R., Tang, D. & Liu, J. Ferroptosis: principles and significance in health and disease. J. Hematol. Oncol. 17 , 41 (2024). Article CAS PubMed PubMed Central Google Scholar Stockwell, B. R. et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171 , 273–285 (2017). Article CAS PubMed PubMed Central Google Scholar Brown, A. R., Hirschhorn, T. & Stockwell, B. R. Ferroptosis-disease perils and therapeutic promise. Science 386 , 848–849 (2024). Article ADS CAS PubMed Google Scholar Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156 , 317–331 (2014). Article CAS PubMed PubMed Central Google Scholar Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575 , 693–698 (2019). Article ADS CAS PubMed Google Scholar Bersuker, K. et al. …