ArticleInflammatory bowel diseases2013
Antioxidant properties of mesalamine in colitis inhibit phosphoinositide 3-kinase signaling in progenitor cells.
Article in Inflammatory bowel diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- A review of the biological and pharmacological activities of mesalazine or 5-aminosalicylic acid (5-ASA): an anti-ulcer and anti-oxidant drug.Inflammopharmacology · 2021Pooled it
- Myo-inositol reduces β-catenin activation in colitis.World journal of gastroenterology · 2017Trial
- Trial
- Eosinophils in inflammatory bowel disease pathogenesis: an ROS-centric view.Frontiers in allergy · 2025Article
- Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy.Diseases (Basel, Switzerland) · 2024Article
- Does caffeine have a double-edged sword role in inflammation and carcinogenesis in the colon?Intestinal research · 2023Review
- Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer.Molecules (Basel, Switzerland) · 2023Review
- From inflammatory bowel disease to colorectal cancer: what's the role of miRNAs?Cancer cell international · 2022Review
- Mesalamine-Mediated Amelioration of Experimental Colitis in Piglets Involves Gut Microbiota Modulation and Intestinal Immune Cell Infiltration.Frontiers in immunology · 2022Article
- Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor.Frontiers in physiology · 2021Review
- Preparation of MSZ Hydrogel and Its Treatment of Colitis.Frontiers in pharmacology · 2021Article
- Acetylsalicylic acid-tris-hydroxymethyl-aminomethane reduces colon mucosal damage without causing gastric side effects in a rat model of colitis.Inflammopharmacology · 2018Article
- ROS in gastrointestinal inflammation: Rescue Or Sabotage?British journal of pharmacology · 2017Review
- Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer.Inflammatory bowel diseases · 2015Article
- Five-aminosalicylic Acid: an update for the reappraisal of an old drug.Gastroenterology research and practice · 2015Review
- Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease.World journal of gastroenterology · 2014Review
- The effect of 5-aminosalicylic acid on renal ischemia-reperfusion injury in rats.Indian journal of pharmacologyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMesalamine, 5-aminosalicylic acid (5-ASA), is a potent antioxidant and is known to enhance peroxisome proliferator-activated receptor γ activity in the intestine. Our previous studies suggested reduced Phosphoinositide 3-Kinase (PI3K)/β-catenin signaling as a mechanism for 5-ASA chemoprevention in chronic ulcerative colitis (CUC). We now hypothesize that 5-ASA mediates changes in intestinal epithelial cell (IEC) reactive oxygen species during colitis to affect phosphatase and tensin homolog (PTEN), PI3K, and β-catenin signaling.
methodsHere, we examined effects of 5-ASA on oxidant-induced cell signaling pathways in HT-29 cells, IECs from mice, and biopsy tissue from control and CUC patients. Samples were selected to control for inflammation between untreated and 5-ASA-treated CUC patients.
resultsDirect evaluation of IEC in H2O2-stimulated whole colonic crypts indicated that 5-ASA reduces reactive oxygen species levels in lower crypt IECs where long-lived progenitor cells reside. Analysis of biopsies from patient samples revealed that 5-ASA increases expression of the antioxidant catalase in CUC patients. Also, 5-ASA increased nuclear peroxisome proliferator-activated receptor γ protein and target gene expression. Data showed 5-ASA-induced peroxisome proliferator-activated receptor γ DNA binding to the PTEN promoter (chromatin immunoprecipitation) and reduced both phosphorylated and oxidized (inactive) PTEN protein levels. Analysis of patient samples revealed 5-ASA that also reduced levels of active phosphorylated Akt in inflamed colitis tissue. Reduced PI3K/Akt signaling and expression of β-catenin target genes in 5-ASA-treated CUC patients additionally suggests enhanced PTEN activity as well.
conclusionsTherefore, 5-ASA reduces CUC-induced reactive oxygen species in colonic progenitor cells and enhances PTEN activity, thus attenuating PI3K/Akt signaling. These data suggest that the antioxidant properties of 5-ASA may be the predominant mechanism for 5-ASA chemoprevention.
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