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- Title
- Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death
- Author(s)
- M Y Kwon; E Park; Seon-Jin Lee; S W Chung
- Bibliographic Citation
- Oncotarget, vol. 6, no. 27, pp. 24393-24403
- Publication Year
- 2015
- Abstract
- The oncogenic RAS-selective lethal small molecule Erastin triggers a unique iron-dependent form of nonapoptotic cell death termed ferroptosis. Ferroptosis is dependent upon the production of intracellular iron-dependent reactive oxygen species (ROS), but not other metals. However, key regulators remain unknown. The heme oxygenase (HO) is a major intracellular source of iron. In this study, the role of heme oxygenase in Erastin-triggered ferroptotic cancer cell death has been investigated. Zinc protoporphyrin IX (ZnPP), a HO-1 inhibitor, prevented Erastin-triggered ferroptotic cancer cell death. Furthermore, Erastin induced the protein and mRNA levels of HO-1 in HT-1080 fibrosarcoma cells. HO-1+/+ and HO-1-/- fibroblast, HO-1 overexpression, and chycloheximide-treated experiments revealed that the expression of HO-1 has a decisive effects in Erastin-triggered cell death. Hemin and CO-releasing molecules (CORM) promote Erastin-induced ferroptotic cell death, not by biliverdin and bilirubin. In addition, hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death.
- Keyword
- Free radicalsHeme oxygenase-1IronOncogeneOncology
- ISSN
- 1949-2553
- Publisher
- Impact Journals
- DOI
- http://dx.doi.org/10.18632/oncotarget.5162
- Type
- Article
- Appears in Collections:
- Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
- Files in This Item:
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