Pristimerin suppresses colorectal cancer through inhibiting inflammatory responses and Wnt/β-catenin signaling

  • Toxicol Appl Pharmacol. 2020 Jan 1;386:114813. doi: 10.1016/j.taap.2019.114813.
Qun Zhao  1 ,  Yun Bi  2 ,  Jing Zhong  3 ,  Ziting Ren  2 ,  Yingxiang Liu  2 ,  Junjun Jia  2 ,  Mengting Yu  2 ,  Yan Tan  2 ,  Qiufang Zhang  2 ,  Xianjun Yu  4
Affiliations
  • 1. Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China.
  • 2. Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China.
  • 3. Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China; Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
  • 4. Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China. Electronic address: [email protected].
PMID: 31715269 DOI: 10.1016/j.taap.2019.114813
Abstract

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/β-catenin signaling by RNA-Seq. Pristimerin inhibited Wnt/β-catenin signaling via activation of GSK3β, thereby suppressing Wnt target gene expression in colon Cancer HCT116 and HT-29 cells. In HCT116 colon Cancer xenografts and APCmin/+ mice, which undergo spontaneous intestinal tumorigenesis, administration of pristimerin reduced the tumor progression and decreased the expression of phosphorylated GSK3β Ser 9, β-catenin, cyclin D1 and c-Myc. These results suggest that pristimerin is a potent agent for preventing colon inflammation and carcinogenesis.

Keywords
Colorectal cancer; Murine models; Pristimerin; Wnt/β-catenin.
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