ArticlePloS one2013
Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Regulating ferroptosis: the impact of stevia on alleviating liver damage in streptozotocin-induced diabetic rats.Molecular biology reports · 2026Article
- Targeting Interleukin-6 for Treatment of CKD and Cardiovascular Disease.Kidney international reports · 2026Review
- Proteomic Differentiation of Colorectal Cancer From Normal Tissue via Ex Vivo E-Biopsy: A Novel Approach to Molecular Sampling for Diagnostic Precision.Cancer medicine · 2026Article
- Therapeutic Potential of Kinkeliba (Molecules (Basel, Switzerland) · 2026Article
- Iron deficiency without anemia: An underrecognized and undertreated clinical condition with special focus on colorectal cancer.Clinical hematology international · 2026Review
- Review
- Macrophage Metabolic Reprogramming in Inflammatory Bowel Diseases: From Pathogenesis to Therapy.Journal of inflammation research · 2025Review
- Identification and Characterization of Oxidative Stress and Endoplasmic Reticulum Stress-Related Genes in Esophageal Cancer.Journal of Cancer · 2025Article
- Association between serum iron status and the risk of colorectal cancer in US adults: a cross-sectional analysis of NHANES 2001-2020.BMC gastroenterology · 2024Article
- The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells.Scientific reports · 2024Article
- Article
- Non-Invasive Zinc Protoporphyrin Screening Offers Opportunities for Secondary Prevention of Iron Deficiency in Blood Donors.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2023Article
- Myeloid FTH1 Deficiency Protects Mice From Colitis and Colitis-associated Colorectal Cancer via Reducing DMT1-Imported Iron and STAT3 Activation.Inflammatory bowel diseases · 2023Article
- Iron metabolism in colorectal cancer.Frontiers in oncology · 2023Review
- Iron accelerates Fusobacterium nucleatum-induced CCL8 expression in macrophages and is associated with colorectal cancer progression.JCI insight · 2022Article
- Supplementation with High or Low Iron Reduces Colitis Severity in an AOM/DSS Mouse Model.Nutrients · 2022Article
- Aberrant Expression TFR1/CD71 in Gastric Cancer Identifies a Novel Potential Prognostic Marker and Therapeutic Target.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The JMJD Family Histone Demethylases in Crosstalk Between Inflammation and Cancer.Frontiers in immunology · 2022Review
- Intravenous iron is non-inferior to oral iron regarding cell growth and iron metabolism in colorectal cancer associated with iron-deficiency anaemia.Scientific reports · 2021Article
- Oral and Intravenous Iron Therapy Differentially Alter the On- and Off-Tumor Microbiota in Anemic Colorectal Cancer Patients.Cancers · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic intestinal inflammation and high dietary iron are associated with colorectal cancer development. The role of Stat3 activation in iron-induced colonic inflammation and tumorigenesis was investigated in a mouse model of inflammation-associated colorectal cancer. Mice, fed either an iron-supplemented or control diet, were treated with azoxymethane and dextran sodium sulfate (DSS). Intestinal inflammation and tumor development were assessed by endoscopy and histology, gene expression by real-time PCR, Stat3 phosphorylation by immunoblot, cytokines by ELISA and apoptosis by TUNEL assay. Colonic inflammation was more severe in mice fed an iron-supplemented compared with a control diet one week post-DSS treatment, with enhanced colonic IL-6 and IL-11 release and Stat3 phosphorylation. Both IL-6 and ferritin, the iron storage protein, co-localized with macrophages suggesting iron may act directly on IL-6 producing-macrophages. Iron increased DSS-induced colonic epithelial cell proliferation and apoptosis consistent with enhanced mucosal damage. DSS-treated mice developed anemia that was not alleviated by dietary iron supplementation. Six weeks post-DSS treatment, iron-supplemented mice developed more and larger colonic tumors compared with control mice. Intratumoral IL-6 and IL-11 expression increased in DSS-treated mice and IL-6, and possibly IL-11, were enhanced by dietary iron. Gene expression of iron importers, divalent metal transporter 1 and transferrin receptor 1, increased and iron exporter, ferroportin, decreased in colonic tumors suggesting increased iron uptake. Dietary iron and colonic inflammation synergistically activated colonic IL-6/IL-11-Stat3 signaling promoting tumorigenesis. Oral iron therapy may be detrimental in inflammatory bowel disease since it may exacerbate colonic inflammation and increase colorectal cancer risk.
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