铁死亡是一种非凋亡形式的受调节细胞死亡，其特征是铁依赖性脂质过氧化。它可由多种机制触发，包括谷胱甘肽过氧化物酶 4 (GPX4)-谷胱甘肽 (GSH) 轴、铁代谢、脂质代谢、GTP 环水解酶 1 (GCH1)-四氢生物蝶呤 (BH4) 途径和铁死亡抑制蛋白 1（ FSP1)-辅酶Q10轴。当细胞发生铁死亡时，氧化还原平衡被破坏，这对癌细胞是致命的。此外，一些肿瘤相关基因参与铁死亡。因此，针对铁死亡可能是治疗癌症的有效策略。一些小分子化合物通过铁死亡表现出抗肿瘤作用，包括索拉非尼和六甲蜜胺，它们分别通过抑制System-Xc和GPX4诱导铁死亡，但仍然存在许多问题，例如成药性差。一些研究表明，许多中药通过抑制GPX4、溶质载体家族7成员11（SLC7A11）和核因子（红细胞衍生2）样2（Nrf2），或通过增加酰基辅酶 A 合成酶长链家族成员 4 (ACSL4)、转铁蛋白 (TF) 和转铁蛋白受体 1 (TFR1)。这些变化可导致铁蛋白的溶酶体降解、铁的积累、脂质过氧化和活性氧（ROS）的产生，进而促进抗肿瘤活性或与化疗药物的协同作用。在本研究中，我们阐明了铁死亡的潜在机制，以及针对铁死亡的中药的抗肿瘤药理学，包括方剂、中药、提取物和天然化合物。我们的研究结果可以为针对铁死亡的抗肿瘤药物的研究提供有价值的参考，特别是那些从中药开发的药物。© 2023。国际中医药与生物医学中心有限公司。

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM.© 2023. International Society for Chinese Medicine and BioMed Central Ltd.