Shi Xingxing, Liu Kun, Tian Yuchang, Bi Xinyi, Zhang Junkai, Ma Fengyi, Wei Wensheng, Zhao Tongbiao
State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
Cell Death Discov. 2025 Jul 7;11(1):309. doi: 10.1038/s41420-025-02598-3.
Huaier (Trametes Robiniophila Murr), a traditional Chinese medicine, has emerged as a promising therapeutic agent against cancers in clinical settings, yet its underlying mechanisms remain elusive. In this study, we demonstrate that Huaier effectively suppresses lung cancer by inducing ferroptosis. Mechanistically, Huaier simultaneously and independently downregulates the antioxidant pathway SLC7A11/GPX4 and elevates intracellular iron levels through NCOA4-mediated ferritinophagy degradation of FTH1 in lung cancer cells. Both the iron chelator deferoxamine (DFO) and the ferroptosis inhibitor ferrostatin-1 (Fer-1) mitigate Huaier-induced cell death. In both urethane-induced lung tumorigenesis models and cell-derived xenograft (CDX) models, Huaier significantly inhibits tumor progression by inducing ferroptosis, which can be counteracted by SRS16-86. Our study uncovers a novel mechanism by which Huaier induces ferroptosis to suppress lung cancer, underscoring its potential as a therapeutic agent for lung cancer or as part of a combination therapy strategy.
槐耳（槐栓菌）是一种传统中药，在临床环境中已成为一种有前景的抗癌治疗药物，但其潜在机制仍不清楚。在本研究中，我们证明槐耳通过诱导铁死亡有效抑制肺癌。机制上，槐耳同时且独立地下调抗氧化途径SLC7A11/GPX4，并通过NCOA4介导的肺癌细胞中FTH1的铁蛋白自噬降解来提高细胞内铁水平。铁螯合剂去铁胺（DFO）和铁死亡抑制剂铁抑素-1（Fer-1）均减轻槐耳诱导的细胞死亡。在氨基甲酸乙酯诱导的肺肿瘤发生模型和细胞来源异种移植（CDX）模型中，槐耳通过诱导铁死亡显著抑制肿瘤进展，而SRS16-86可抵消这种作用。我们的研究揭示了槐耳诱导铁死亡以抑制肺癌的新机制，突出了其作为肺癌治疗药物或联合治疗策略一部分的潜力。
