Silibinin suppresses spontaneous tumorigenesis in APC min/+ mouse model by modulating beta-catenin pathway

Pharm Res. 2009 Dec;26(12):2558-67. doi: 10.1007/s11095-009-9968-1. Epub 2009 Sep 25.


Purpose: Here we assessed whether silibinin, a nontoxic chemopreventive agent, inhibits spontaneous intestinal tumorigenesis in APC ( min/+) mouse model, a genetically predisposed animal model of human familial adenomatous polyposis (FAP).

Materials and methods: Six-week-old APC (min/+) mice were divided into four groups and orally gavaged with 0.2 ml vehicle, or 250, 500 and 750 mg silibinin/kg body weight in 0.2 ml vehicle for five days/week. After 6 weeks, polyp burden was analyzed and tissues examined for molecular alterations.

Results: Silibinin treatments decreased total number of intestinal polyps by 34% (P < 0.01), 42% (P < 0.01) and 55% (P < 0.001), respectively. Immunohistochemical analysis showed that silibinin dose-dependently decreases (P < 0.001) proliferation and induces (P < 0.001) apoptosis only in intestinal polyps without any considerable effects on normal crypt-villi in APC (min/+) or wild-type mice. Further analysis of polyps showed that silibinin decreases beta-catenin, cyclin D1, c-Myc and phospho-glycogen synthase kinase-3beta expression. Silibinin treatment also decreased phospho-Akt, cyclooxygenase-2, inducible nitric oxide synthase, nitrotyrosine and nitrite levels in polyps, the well-known mediators of intestinal/colon carcinogenesis.

Conclusion: Together, these results establish silibinin efficacy in a well-established genetic model of FAP, APC (min/+) mouse, and suggest that this natural agent modulates various molecular pathways including beta-catenin in its overall chemopreventive efficacy against intestinal carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Animals
  • Antioxidants / pharmacology
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / prevention & control
  • Male
  • Mice
  • Mutation / genetics
  • Signal Transduction / drug effects
  • Silybin
  • Silymarin / pharmacology
  • beta Catenin / metabolism*


  • Adenomatous Polyposis Coli Protein
  • Antioxidants
  • Silymarin
  • beta Catenin
  • Silybin