Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 386, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2019.114813
Keywords
Pristimerin; Colorectal cancer; Murine models; Wnt/beta-catenin
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Funding
- National Natural Science Foundation of China [81502548, 81902852]
- Natural Science Foundation of Hubei Provincial Department of Education [D20182101]
- Foundation of Health Commission of Hubei Province [WJ2019M053]
- Biomedical Research Foundation, Hubei University of Medicine [HBMUPI201809]
- Foundation for Innovative Research Team of Institute of Medicine and Nursing, Hubei University of Medicine [2017YHKT01]
- Scientific and Technological Project of Shiyan City of Hubei Province [18Y02]
- Hubei University of Medicine [2018QDJZR06]
- Student's Platform for Innovation and Entrepreneurship Training Program [201810929019, 201810929058]
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Pristimerin, a triterpenoid, has exhibited potential anti-inflammatory and anti-tumor activities. Nevertheless, the role and mechanism of pristimerin in intestinal inflammation and colon cancer require further investigation. Here, we found that pristimerin protected mice from dextran sulfate sodium (DSS)-induced colitis, restoring epithelial damage and reducing tissue inflammation and inflammatory cell infiltration. In addition, pristimerin dramatically reduced the number and size of the tumors in a azoxymethane (AOM)/DSS-induced colitis-associated colorectal cancer (CAC) model. Furthermore, we found that pristimerin suppressed Wnt/beta-catenin signaling by RNA-Seq. Pristimerin inhibited Wnt/beta-catenin signaling via activation of GSK3 beta, thereby suppressing Wnt target gene expression in colon cancer HCT116 and HT-29 cells. In HCT116 colon cancer xenografts and APC(min/+) mice, which undergo spontaneous intestinal tumorigenesis, administration of pristimerin reduced the tumor progression and decreased the expression of phosphorylated GSK3 beta Ser 9, beta-catenin, cyclin D1 and c-Myc. These results suggest that pristimerin is a potent agent for preventing colon inflammation and carcinogenesis.
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