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A review on the research progress of traditional Chinese medicine with anti-cancer effect targeting ferroptosis

GPX4 脂质过氧化 癌细胞 转铁蛋白受体 癌症研究 活性氧 化学 姜黄素 癌症 药理学 细胞生物学 生物化学 生物 氧化应激 转铁蛋白 谷胱甘肽过氧化物酶 超氧化物歧化酶 遗传学
作者
Longyan Wang,Huiming Huang,Xingxing Li,Lishan Ouyang,Xuejiao Wei,Jinxin Xie,Dongxiao Liu,Peng Tan,Zhongdong Hu
出处
期刊:Chinese Medicine [BioMed Central]
卷期号:18 (1) 被引量:5
标识
DOI:10.1186/s13020-023-00838-1
摘要

Abstract 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.
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