Cannabinoid Receptor-1 Up-regulation in Azoxymethane (AOM)-treated Mice After Dietary Treatment with Quercetin

Anticancer Res. 2018 Aug;38(8):4485-4491. doi: 10.21873/anticanres.12752.

Abstract

Background/aim: The expression of cannabinoid receptor-1 (CB1-R) seems to be modulated by bioactive natural components such as the flavonoid quercetin. The aim of this study was to determine in an animal model of induced-colon cancer, whether quercetin inhibits colon carcinogenesis through changes in the expression of CB1-R.

Materials and methods: C57BL/6J male mice were randomly assigned to standard diet or experimental diet supplemented with 0.5% quercetin. Azoxymethane (AOM) (10 mg/kg body weight) or saline solution (PBS) was intraperitoneally injected, once weekly for 6 weeks.

Results: The diet supplemented with quercetin induced CB1-R gene expression and protein, inhibiting the protein levels of STAT3 and p-STAT3 (both mediators of cell proliferation). Dietary quercetin also caused a significant increase in Bax/Bcl2 ratio protein expression.

Conclusion: The anti-proliferative and pro-apoptotic effects of quercetin in AOM-treated mice are mediated by induction of the protein and gene expression levels of CB1-R.

Keywords: Cannabinoid receptor-1; azoxymethane (AOM)-mouse model; colorectal cancer; quercetin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Azoxymethane / pharmacology*
  • Carcinogenesis / drug effects
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Diet
  • Dietary Supplements
  • Flavonoids / pharmacology
  • Gene Expression / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quercetin / pharmacology*
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Up-Regulation / drug effects*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Flavonoids
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, Cannabinoid, CB1
  • bcl-2-Associated X Protein
  • Quercetin
  • Azoxymethane