Ferroptosis in the pathogenesis of brain tumors

Abstract

The field of research on ferroptosis has seen an explosive growth in the past few years since the term was coined in 2012. This review highlights the current state of knowledge on the developmental mechanism of this unique mode of cell death, induced by iron-dependent phospholipid peroxidation, which is regulated by a variety of cellular metabolic events, including redox homeostasis. The xCT system, an amino acid antiporter that supports the synthesis of glutathione (GSH) and oxidation protection, is among these factors. The risk of iron accumulation in neurons, astrocytes, oligodendrocytes, microglia, and Schwann cells and the development of oxidative stress are discussed. Ferroptosis triggers a cascade of events including activation of inflammation, oxidation of neurotransmitters, impaired neuronal communication, myelin sheath degeneration, astrocyte dysregulation, dementia, and cell death. On the other hand, the exceptional vulnerability of cancer cells originating from the nervous tissue to ferroptosis is estimated. The evidence is given for the initiation of ferroptosis in tumor cells as a factor inhibiting the growth and promoting the death of these cells. Particular attention is paid to the pharmacological modulation of ferroptosis through its induction and inhibition for the treatment of drug-resistant cancers. The choice of targets for the induction of ferroptosis in cancer cells is discussed. Glutathione peroxidase 4 and xCT amino acid antiporter are recognized as the most preferred targets and the antitumor potential of their inhibition and side effects are evaluated.

Keywords

brain tumors / ferroptosis / glutathione peroxidase 4 / lipid peroxidation

Funding

ФГБОУ ВО «Астраханский ГМУ» Минздрава РоссииAstrakhan State Medical University of the Ministry of Health of Russia

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