Molecular mechanisms of ferroptosis and its role in cancer therapy

• Published in: Journal of cellular and molecular medicine Vol. 23; no. 8; pp. 4900 - 4912
• Main Authors: Xu, Tao, Ding, Wei, Ji, Xiaoyu, Ao, Xiang, Liu, Ying, Yu, Wanpeng, Wang, Jianxun
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2019; John Wiley and Sons Inc
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Autophagy; Cancer therapies; cancer therapy; Cell death; Cell Line, Tumor; Cysteine - metabolism; Drug resistance; Endoplasmic Reticulum Stress - drug effects; Endoplasmic Reticulum Stress - genetics; Enzymes; Fatty Acids, Unsaturated - metabolism; Ferroptosis; Ferroptosis - drug effects; Ferroptosis - genetics; Glutamine - metabolism; Humans; Iron - metabolism; Lipid Peroxidation; Lipids; Lysosomes - enzymology; Lysosomes - genetics; Lysosomes - metabolism; Metabolism; Metabolites; Mitochondria - enzymology; Mitochondria - metabolism; Molecular modelling; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Phospholipid Hydroperoxide Glutathione Peroxidase - antagonists & inhibitors; Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism; programmed cell death; Reagents; Review; Reviews; Signal Transduction - drug effects; Signal Transduction - genetics; small molecules; cancer therapy; ferroptosis; drug resistance; programmed cell death; small molecules
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.14511

Ferroptosis is a newly defined programmed cell death process with the hallmark of the accumulation of iron‐dependent lipid peroxides. The term was first coined in 2012 by the Stockwell Lab, who described a unique type of cell death induced by the small molecules erastin or RSL3. Ferroptosis is distinct from other already established programmed cell death and has unique morphological and bioenergetic features. The physiological role of ferroptosis during development has not been well characterized. However, ferroptosis shows great potentials during the cancer therapy. Great progress has been made in exploring the mechanisms of ferroptosis. In this review, we focus on the molecular mechanisms of ferroptosis, the small molecules functioning in ferroptosis initiation and ferroptosis sensitivity in different cancers. We are also concerned with the new arising questions in this particular research area that remains unanswered.