Journal Article Review Epublish
PubMed: 40733290 DOI: 10.3390/molecules30143020
Ferroptosis and Metabolic Dysregulation: Emerging Chemical Targets in Cancer and Infection.
Molecules 30(14)
Authors: Marta Pawłowska, Jarosław Nuszkiewicz, Dorian Julian Jarek, Alina Woźniak
Affiliations
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St. 85-092 Bydgoszcz, Poland.
- Student Research Club of Medical Biology and Biochemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St. 85-092 Bydgoszcz, Poland.
Abstract
The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in the iron-lipid homeostasis and antioxidant defense, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). Herein, the molecular mechanisms of ferroptosis and its role in the tumorigenesis process and infection-related diseases are presented. It also discusses metabolic reprogramming as a factor that modifies the levels of cell-sensitizing polyunsaturated fatty acids (PUFAs), iron dysregulation, and oxidative stress in aggressive cancers and inflammatory diseases such as sepsis, tuberculosis, and COVID-19. Particular attention is given to chemical modulators of ferroptosis, including synthetic inducers and inhibitors, as well as bioactive natural compounds. Our focus is on the significance of analytical tools, such as lipidomics and metabolomics, in understanding the phenomenon of ferroptosis. Finally, we explore novel therapeutic approaches targeting ferroptosis in cancer and infectious diseases, while navigating both the opportunities and challenges in drug development. The review then draws on chemical biology and disease pathology to propose promising areas of study for ferroptosis-related therapies.
MeSH
Cells, Neoplasms, Ferroptosis, Metabolomics, Therapeutics, Infections, Glutathione