Department of Internal Medicine of Traditional Chinese Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai 200092, China.
Biomed Pharmacother. 2023 Mar;159:114241. doi: 10.1016/j.biopha.2023.114241. Epub 2023 Jan 10.
Ferroptosis is a novel type of programmed cell death, characterized by a dysregulated iron metabolism and accumulation of lipid peroxides. It features the alteration of mitochondria and aberrant accumulation of excessive iron as well as loss of the cysteine-glutathione-GPX4 axis. Eventually, the accumulated lipid peroxides result in lethal damage to the cells. Ferroptosis is induced by the overloading of iron and the accumulation of ROS and can be inhibited by the activation of the GPX4 pathway, FS1-CoQ10 pathway, GCH1-BH4 pathway, and the DHODH pathway, it is also regulated by the oncogenes and tumor suppressors. Ferroptosis involves various physiological and pathological processes, and increasing evidence indicates that ferroptosis play a critical role in cancers and other diseases. It inhibits the proliferation of malignant cells in various types of cancers and inducing ferroptosis may become a new method of cancer treatment. Many inhibitors targeting the key factors of ferroptosis such as SLC7A11, GPX4, and iron overload have been developed. The application of ferroptosis is mainly divided into two directions, i.e. to avoid ferroptosis in healthy cells and selectively induce ferroptosis in cancers. In this review, we provide a critical analysis of the concept, and regulation pathways of ferroptosis and explored its roles in various diseases, we also summarized the compounds targeting ferroptosis, aiming to promote the speed of clinical use of ferroptosis induction in cancer treatment.
铁死亡是一种新型的程序性细胞死亡方式，其特征是铁代谢失调和脂质过氧化物积累。它表现为线粒体的改变和异常积累过量的铁以及半胱氨酸-谷胱甘肽-GPX4 轴的丧失。最终，积累的脂质过氧化物导致细胞致命损伤。铁死亡是由铁过载和 ROS 积累引起的，可以通过激活 GPX4 途径、FS1-CoQ10 途径、GCH1-BH4 途径和 DHODH 途径来抑制，它还受到癌基因和抑癌基因的调节。铁死亡涉及各种生理和病理过程，越来越多的证据表明铁死亡在癌症和其他疾病中起着关键作用。它抑制各种类型癌症中恶性细胞的增殖，诱导铁死亡可能成为癌症治疗的新方法。已经开发出许多针对铁死亡关键因素的抑制剂，如 SLC7A11、GPX4 和铁过载。铁死亡的应用主要分为两个方向，即在健康细胞中避免铁死亡和选择性诱导癌症中的铁死亡。在这篇综述中，我们对铁死亡的概念和调控途径进行了批判性分析，并探讨了其在各种疾病中的作用，我们还总结了针对铁死亡的化合物，旨在促进铁死亡诱导在癌症治疗中的临床应用速度。
