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0This research identifies spermine as a natural iron chelator that serves as a critical internal defense against ferroptosis, a form of iron-dependent cell death. Through metabolic profiling of hepatocellular carcinoma (HCC), scientists discovered that cancer cells exploit an alternative ALDH18A1-mediated pathway to synthesize spermine from glutamine, thereby neutralizing labile iron and preventing lipid peroxidation. While spermine catabolism can produce pro-oxidant byproducts, the metabolite itself directly binds to ferrous iron (Fe2+) to stop the catalytic reactions that drive cellular damage. Experimental data demonstrate that blocking this biosynthetic axis triggers ferroptosis and halts tumor growth, whereas supplementing spermine offers protection against ischaemia–reperfusion injury in vital organs. Ultimately, the study reveals a metabolic vulnerability in liver cancer and highlights the therapeutic potential of modulating polyamine levels to regulate cell survival.
References:
Li M, Yu X, Ouyang S, et al. Spermine is an endogenous iron chelator that inhibits ferroptosis[J]. Nature, 2026: 1-11.
