Chen Heshu, Wang Chenyu, Liu Zemin, He Xinmiao, Tang Wenjie, He Liuqin, Feng Yanzhong, Liu Di, Yin Yulong, Li Tiejun
Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China.
Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China.
Antioxidants (Basel). 2022 Jul 31;11(8):1504. doi: 10.3390/antiox11081504.
Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.
铁死亡是一种新型的非凋亡性细胞死亡方式，与其他细胞死亡模式不同，主要在肿瘤细胞中被发现。先前的研究报道，铁死亡可由特定的调节剂（如药物、营养物质和铁螯合剂）触发，导致细胞内脂质活性氧（ROS）积累增加和铁过载。最近的报道表明，细胞和机体水平的铁死亡可以预防炎症风暴和癌症发展。新出现的证据表明，潜在机制（如系统Xc-、谷胱甘肽过氧化物酶4（GPX4）、脂质过氧化、谷胱甘肽（GSH）和铁螯合剂）参与了铁死亡，这可能介导氧化应激和铁过载等生物学过程来治疗癌症。迄今为止，至少有三条途径介导癌细胞中的铁死亡：系统Xc-/GSH/GPX4、FSP1/CoQ10/NAD(P)H和ATG5/ATG7/NCOA4。在此，我们总结了在癌症背景下铁死亡发生和发展的最新进展、铁死亡与各种调节剂之间的关联以及针对铁死亡治疗癌症的潜在机制和治疗策略。
