ArticleCell death & disease2020
Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 85 citations in OpenAlex.
- Review
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- DcR3 Suppresses Lipopolysaccharide-Induced Aggresome-like Structures in Macrophages via Inhibition of Reactive Oxygen Species and p38 MAPK.International journal of molecular sciences · 2026Article
- Nanoparticle-mediated targeted delivery of lutein for retinal protection: emerging strategies in ocular drug targeting.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A HO-1 gene knockout using a NanoCRISPR scaffold suppresses metastasis in mouse models.Nature biomedical engineering · 2026Article
- Cellular Senescence Triggered by Food and Environmental Genotoxins.International journal of molecular sciences · 2026Review
- Epithelial HO-1 regulates iron availability and promotes colonic tumorigenesis in a context-dependent manner.JCI insight · 2026Article
- Estrobolome dysbiosis in canine mammary gland tumors:Frontiers in microbiology · 2026Article
- Microbiota-miR-101 interactions in obesity-associated colorectal cancer: from barrier dysfunction to precision therapeutic strategies.Frontiers in pharmacology · 2026Review
- Dual-Function Role of Phenolated Albumin in Hemin-Mediated Hydrogel Formation.Gels (Basel, Switzerland) · 2025Article
- Synthesis of nanoparticles of cobalt protoporphyrin IX (Co(iii)PPIX NPs). Antiradical, cytotoxicity and antibacterial properties.RSC advances · 2025Article
- The Interplay Between the Gut Microbiota and Colorectal Cancer: A Review of the Literature.Microorganisms · 2025Review
- New Insights into Aspirin's Anticancer Activity: The Predominant Role of Its Iron-Chelating Antioxidant Metabolites.Antioxidants (Basel, Switzerland) · 2024Review
- New insights into crosstalk between Nrf2 pathway and ferroptosis in lung disease.Cell death & disease · 2024Review
- Genetics, diet, microbiota, and metabolome: partners in crime for colon carcinogenesis.Clinical and experimental medicine · 2024Review
- Targeting PARP-1 and DNA Damage Response Defects in Colorectal Cancer Chemotherapy with Established and Novel PARP Inhibitors.Cancers · 2024Article
- Examining Hemin and its Derivatives: Induction of Heme-Oxygenase-1 Activity and Oxidative Stress in Breast Cancer Cells through Collaborative Experimental Analysis and Molecular Dynamics Simulations.Journal of medicinal chemistry · 2024Article
- CCN1-Mediated Signaling in Placental Villous Tissues after SARS-CoV-2 Infection in Term Pregnant Women: Implications for Dysregulated Angiogenesis.Current issues in molecular biology · 2024Article
- Pathological significance of heme oxygenase-1 as a potential tumor promoter in heme-induced colorectal carcinogenesis.Cancer pathogenesis and therapy · 2024Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The consumption of red meat is probably carcinogenic to humans and is associated with an increased risk to develop colorectal cancer (CRC). Red meat contains high amounts of heme iron, which is thought to play a causal role in tumor formation. In this study, we investigated the genotoxic and cytotoxic effects of heme iron (i.e., hemin) versus inorganic iron in human colonic epithelial cells (HCEC), human CRC cell lines and murine intestinal organoids. Hemin catalyzed the formation of reactive oxygen species (ROS) and induced oxidative DNA damage as well as DNA strand breaks in both HCEC and CRC cells. In contrast, inorganic iron hardly affected ROS levels and only slightly increased DNA damage. Hemin, but not inorganic iron, caused cell death and reduced cell viability. This occurred preferentially in non-malignant HCEC, which was corroborated in intestinal organoids. Both hemin and inorganic iron were taken up into HCEC and CRC cells, however with differential kinetics and efficiency. Hemin caused stabilization and nuclear translocation of Nrf2, which induced heme oxygenase-1 (HO-1) and ferritin heavy chain (FtH). This was not observed after inorganic iron treatment. Chemical inhibition or genetic knockdown of HO-1 potentiated hemin-triggered ROS generation and oxidative DNA damage preferentially in HCEC. Furthermore, HO-1 abrogation strongly augmented the cytotoxic effects of hemin in HCEC, revealing its pivotal function in colonocytes and highlighting the toxicity of free intracellular heme iron. Taken together, this study demonstrated that hemin, but not inorganic iron, induces ROS and DNA damage, resulting in a preferential cytotoxicity in non-malignant intestinal epithelial cells. Importantly, HO-1 conferred protection against the detrimental effects of hemin.
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