The Mechanism of Ferroptosis and Applications in Tumor Treatment

Abstract

Iron-dependent ferroptosis is a new form of cell death in recent years, which is driven by lipid peroxidation. The lethal lipid accumulation caused by glutathione depletion or inactivation of glutathione peroxidase 4 (GPX4) is characteristic of the ferroptosis process. In recent years, with the in-depth study of ferroptosis, various types of diseases have been reported to be related to ferroptosis. In other words, ferroptosis, which has attracted widespread attention in the fields of biochemistry, oncology, and especially materials science, can undoubtedly provide a new way for patients. This review introduces the relevant mechanisms of ferroptosis, the relationship between ferroptosis and various cancers, as well as the application of ferroptosis in tumor treatment. We also sorted out the genes and drugs that regulate ferroptosis. Moreover, small molecule compound-induced ferroptosis has a strong inhibitory effect on tumor growth in a drugresistant environment, which can enhance the sensitivity of chemotherapeutic drugs, suggesting that ferroptosis is very important in the treatment of tumor drug resistance, but the details are still unclear. How to use ferroptosis to fight cancer, and how to prevent drug-resistant tumor cells have become the focus and direction of research. At the end of the article, some existing problems related to ferroptosis are summarized for future research.

Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation

“…Ferroptosis is a newly discovered form of cell death, which is characterized by the iron-dependent accumulation of lipid reactive oxygen species (ROS). 6 Emerged reports reveal that cancer treatment options based on the induction of ferroptosis effectively eliminate the number of cancer cells. Sorafenib, which induces the induction of ferroptosis, has been approved by the FDA to treat hepatocellular carcinoma (HCC).…”

“…Ferroptosis is a recently discovered unique form of programmed cell death driven by mitochondrial lipid peroxidation and dysregulation of cellular iron metabolism. 6 Unlike necroptosis or apoptosis, ferroptosis is independent of receptor-interacting protein 1 (RIPK1) kinase activity and caspase activity. 7 With the in-depth study, multiple lines have indicated that ferroptosis is related to various types of diseases, especially carcinoma.…”

“… 8–10 Emerged reports reveal that ferroptosis facilitates the selective eradication of cancer cells. 6 , 10 However, investigations regarding the function of ferroptosis in EC progression are still rare.…”

Epigenetic Regulation and Nonepigenetic Mechanisms of Ferroptosis Drive Emerging Nanotherapeutics in Tumor

“…Specific induction of ferroptosis in tumor cells has become a novel target for tumor therapy. Ferroptosis induced by small molecular compounds can evade chemotherapeutic drug resistance and induce the death of cancer cells under the condition that some classical chemotherapeutic drugs have no effects [ 4 ]. The application of nanobiology technology in the efficient delivery of antitumor drugs conforms to the biological characteristics of tumors to a certain extent with great advantages in the efficiency of drug delivery.…”

“…Ferroptosis is an important form of RCD, caused by the accumulation of lipid free radicals dependent on iron ions, and is lucubrated more extensively in the mechanism of cancer treatment [ 3 ]. Ferroptosis is involved in the occurrence and evolution of a variety of diseases, such as tumor [ 4 ], ischemia reperfusion injury (IRI) [ 5 ], renal failure [ 6 ], neurological diseases [ 7 ], and hematological diseases [ 8 ]. Especially in cancer research, ferroptosis can induce the death of various tumor cells, including in liver cancer, pancreatic cancer, and breast cancer, but its mechanism remains to be further explored [ 9 – 12 ].…”