M10, a novel derivative of Myricetin, prevents ulcerative colitis and colorectal tumor through attenuating robust endoplasmic reticulum stress

Carcinogenesis
Feng WangShu-Xiang Cui

Abstract

Chronic gut inflammation disposes to an increased risk of colitis-associated cancer. Chemoprevention is an attractive complementary strategy. We aimed to evaluate the chemopreventive effects of M10, a novel derivative of Myricetin, in the murine azoxymethane/dextran sodium sulfate model. Oral administration of M10 at 50-100 mg/kg once a day for consecutive 12 weeks significantly prevented ulcerative colitis (UC) and colorectal tumor. Pathological analysis of intestines showed that M10 reduced the degree of chronic inflammation and prevented the progression of colorectal tumorigenesis. Flow cytometry analysis of the immunocytes isolated from intraepithelial and lamina propria showed that M10 prevented the infiltration of myeloid-derived suppressor cells and increased CD8+T and CD4+T cells in colorectal tissues. Enzyme-linked immunosorbent analysis revealed the reduction of pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor/macrophage colony-stimulating factor, IL-6 and TNF-α in colonic mucosa. Western blot assay also showed M10 prevention of the NF-κB/IL-6/STAT3 pathways and the biomarkers of inflammation and colorectal tumorigenesis. Electron microscopy analysis revealed that M10 prevent robust endoplas...Continue Reading

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Citations

Apr 25, 2019·Oxidative Medicine and Cellular Longevity·Lucas Martins FrançaAntonio Marcus de Andrade Paes
Jan 10, 2021·Life Sciences·Md Abdul AzizZhang Hongjie
Jan 19, 2020·Current Opinion in Biotechnology·Ruisong PeiBradley Bolling
Jun 3, 2021·Cancers·Sophia Fotiou MagkoutaIoannis Theodorou Kalomenidis
Dec 30, 2021·Pharmacology Research & Perspectives·Mengmeng LiHao Jiang

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