Program

PO2-6-19

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

[Speaker] Shuxiang Cui:1
[Co-author] Feng Wang:1, Zhiyu Song:2, Wenbao Li:3
1:Beijing Key Laboratory of Environmental Toxicology, Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China, 2:Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China, 3:Marine Biomedical Research Institute of Qingdao, Qingdao, China

Background: Inflammatory bowel disease is an important risk factor for colorectal cancer (CRC). There is currently no cure for colitis and CRC. M10 is a novel derivative of Myricetin by adding a hydrophilic group in its structure. Our pilot study showed that M10 prevented colitis in mice more efficacy than Myricetin. We aimed to evaluate the efficacy as well as the mechanism of M10 as a chemopreventive agent against colitis and CRC.
Methods: C57BL/6 mice were exposed to AOM/DSS to induce ulcerative colitis and colorectal tumorigenesis. M10 was given by oral for consecutive 12 weeks. Mice were sacrificed and colorectums were removed for analyzing the degree of inflammation and tumorigenesis.
Results: M10 exhibited stronger activities against colitis and colorectal tumorigenesis than Aspirin. Pathology analysis showed that M10 effectively reduced the degree of chronic inflammation and inhibited the progression of colorectal tumorigenesis. M10 prevented the infiltration of myeloid-derived suppressor cells (MDSCs) and pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-a in intraepithelial and lamina propria tissues. M10 blocked the NF-kB/IL-6/STAT3 pathways. Further analysis suggested that M10 prevented colitis and tumorigenesis through attenuating robust endoplasmic reticulum (ER) stress. M10 inhibited robust ER-stress-mediated autophagy and apoptosis in colonic mucosal cells.
Conclusion: Our findings suggest that M10 could be a promising regimen in chemoprevention against colitis and tumorigenesis.
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