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Review
. 2018 Jul;16(7):1073-1076.
doi: 10.1158/1541-7786.MCR-18-0055. Epub 2018 Mar 28.

Ferroptosis-Induced Endoplasmic Reticulum Stress: Cross-talk Between Ferroptosis and Apoptosis

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Free PMC article
Review

Ferroptosis-Induced Endoplasmic Reticulum Stress: Cross-talk Between Ferroptosis and Apoptosis

Young-Sun Lee et al. Mol Cancer Res. .
Free PMC article

Abstract

Since its discovery in 2012, ferroptosis has been well characterized by the accumulation of lipid peroxides due to the failure of glutathione-dependent antioxidant defenses. It is known as an iron-dependent form of programmed cell death, which is distinct from other forms of cell death such as apoptosis and necrosis. Nonetheless, little is known about the ferroptotic agent-induced endoplasmic reticulum (ER) stress response and its role in cell death. Recent studies reveal that the ferroptotic agent-induced ER stress response plays an important role in the cross-talk between ferroptosis and other types of cell death. Ferroptotic agents induce the unfolded protein response and subsequently ER stress-mediated activation of the PERK-eIF2α-ATF4-CHOP pathway. CHOP (C/EBP homologous protein) signaling pathway-mediated p53-independent PUMA (p53 upregulated modulator of apoptosis) expression is involved in the synergistic interaction between ferroptosis and apoptosis. This review highlights the recent literature on ferroptotic and apoptotic agent interactions through the ER stress-mediated PERK-eIF2α-ATF4-CHOP-PUMA pathway and implicates combined treatment to effectively enhance tumoricidal efficacy as a novel therapeutic strategy for cancer. Mol Cancer Res; 16(7); 1073-6. ©2018 AACR.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Microarray assay for detection of ART-induced gene expression
Human colon cancer HCT116 cells were treated with 50 µM ART for 24 h and triplicate Illumina gene expression microarrays were performed with BeadArray microarray technology.
Figure 2
Figure 2. Schematic diagram of ferroptotic agent-induced ER stress and its role in the interplay between ferroptosis and apoptosis
Schematic diagram of ferroptotic agent-induced ER stress and its role in the interplay between ferroptosis and apoptosis

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