Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death
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// Min-Young Kwon 1 , Eunhee Park 1 , Seon-Jin Lee 2, * , Su Wol Chung 1, * 1 School of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, South Korea 2 Genome Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, South Korea * These authors have contributed equally to this work Correspondence to: Su Wol Chung, e-mail: swchung@ulsan.ac.kr Seon-Jin Lee, e-mail: sjlee@kribb.re.kr Keywords: heme oxygenase-1, oncology, oncogene, iron, free radicals Received: March 11, 2015 Accepted: August 28, 2015 Published: September 10, 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.
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HO-1 is induced upon erastin treatment and accelerates erastin-induced ferroptosis.
“the iron-containing heme oxygenase-1 (HO-1) was reported to be induced upon erastin treatment and to accelerate erastin-induced ferroptosis[87]”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [87]
HO-1 may be a source of iron driving lipid peroxidation during ferroptosis, at least in response to erastin.
“thus, HO-1 may be a source of iron driving the lipid peroxidation that occurs during ferroptosis, at least in response to erastin.”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [87]
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- Authors
- Kwon, M.-Y., Park, E., Lee, S.-J., & Chung, S. W.
- Affiliations
- University of Ulsan (KR)
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Corresponding author
- Lee, Seon-Jin
- Chung, Su Wol
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2015-09-10
- Volume
- 6
- Issue
- 27
- Pages
- 24393-24403
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4695193
- OpenAlex
- W2180777157
- Cited by
- 612
- References
- 30
- Citations by year
- 2026: 47 · 2025: 55 · 2024: 90 · 2023: 91 · 2022: 104 · 2021: 89 · 2020: 46 · 2019: 36 · 2018: 18 · 2017: 26 · 2016: 9 · 2015: 1
- FWCI
- 14.24
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KRIBB Repository (submittedVersion)
- Funders
- National Research Foundation (2014R1A6A1030318, 2012M3A9C3048686)
- National Research Foundation of Korea (2014R1A6A1030318)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- heme oxygenase-1, ferroptosis, erastin, iron-dependent cell death, zinc protoporphyrin, hemin, CO-releasing molecules, lipid peroxidation, reactive oxygen species, cancer cell death, HT1080 fibrosarcoma cells
- MeSH terms
- Animals, Bilirubin, Biliverdine, Cell Nucleus, Cycloheximide, Fibroblasts, Hemin, Humans, Iron, Membrane Proteins, Mice, Inbred BALB C, Mice, Transgenic, Piperazines, Protoporphyrins, Lipid Peroxidation, Gene Expression Regulation, Neoplastic, Cell Death, Reactive Oxygen Species, Gene Expression Profiling, Cell Line, Tumor, Mice, Heme Oxygenase-1
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