ArticlePloS one2015
Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Colorectal Neoplasia Pathogenesis in Normal Appearing Colonic Mucosa -A Perspective With Focus on Eicosanoid Signaling Pathways.Cancer medicine · 2025Review
- Regulating arachidonic acid metabolism: a novel strategy to prevent colorectal inflammatory cancer transformation.Journal of Cancer · 2025Review
- Causal links between circulatory inflammatory cytokines and risk of digestive polyps: a Mendelian randomization analysis.Frontiers in pharmacology · 2024Article
- Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review).International journal of molecular medicine · 2023Review
- Toxoplasma gondii Infection Decreases Intestinal 5-Lipoxygenase Expression, while Exogenous LTBInfection and immunity · 2022Article
- Zileuton inhibits arachidonate-5-lipoxygenase to exert antitumor effects in preclinical cervical cancer models.Cancer chemotherapy and pharmacology · 2021Article
- Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled.Cells · 2021Review
- Molecular Targets in Precision Chemoprevention of Colorectal Cancer: An Update from Pre-Clinical to Clinical Trials.International journal of molecular sciences · 2020Review
- Role of myeloid-derived suppressor cells in the promotion and immunotherapy of colitis-associated cancer.Journal for immunotherapy of cancer · 2020Review
- Article
- Leukotrienes in Tumor-Associated Inflammation.Frontiers in pharmacology · 2020Review
- Arachidonic Acid Metabolism and Kidney Inflammation.International journal of molecular sciences · 2019Review
- Death-Domain-Receptor 3 Deletion Normalizes Inflammatory Gene Expression and Prevents Ileitis in Experimental Crohn's Disease.Inflammatory bowel diseases · 2019Article
- Eicosanoid signaling in carcinogenesis of colorectal cancer.Cancer metastasis reviews · 2018Review
- Leukotriene receptors as potential therapeutic targets.The Journal of clinical investigation · 2018Review
- Cysteinyl Leukotriene Receptor Antagonists Inhibit Migration, Invasion, and Expression of MMP-2/9 in Human Glioblastoma.Cellular and molecular neurobiology · 2018Article
- The yin and yang of leukotriene BSeminars in immunology · 2017Review
- Regulation of inflammation by lipid mediators in oral diseases.Oral diseases · 2017Review
- Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway.International journal of molecular sciences · 2017Review
- Polyunsaturated Fatty Acids and Their Derivatives: Therapeutic Value for Inflammatory, Functional Gastrointestinal Disorders, and Colorectal Cancer.Frontiers in pharmacology · 2016Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
purposeLeukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD) have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO), the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APCΔ468 mice. EXPERIMENTAL
designIn the current study, we inhibited 5-LO by dietary administration of Zileuton in the APCΔ468 mouse model of polyposis and analyzed the effect of in vivo 5-LO inhibition on tumor-associated and systemic inflammation.
resultsZileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4), product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.
conclusionsThis study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.
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