Effective suppression of azoxymethane-induced aberrant crypt foci formation in mice with citrus peel flavonoids

Mol Nutr Food Res. 2013 Mar;57(3):551-5. doi: 10.1002/mnfr.201200606. Epub 2013 Jan 10.

Abstract

Citrus peel or its extract has been reported to exhibit a broad spectrum of biological activity. Herein, we report the first investigation of inhibitory effects of a formulated product from citrus peel extract, gold lotion (GL), on azoxymethane-induced colonic tumorigenesis. We have demonstrated that oral feeding of GL decreased the number of aberrant crypt foci (ACF), particularly large size of ACF in colonic tissues of mice. Both gene and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were suppressed by GL treatment. The in vivo data have revealed for the first time that the citrus peel extract-GL-is an effective antitumor agent mechanistically downregulating the protein levels of iNOS, COX-2, ornithine decarboxylase, vascular endothelial growth factor, and matrix metallopeptidase 9 in colonic tissues of mice, suggesting that GL is a novel functional natural product capable of preventing inflammation-associated colon tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aberrant Crypt Foci / chemically induced
  • Aberrant Crypt Foci / drug therapy*
  • Aberrant Crypt Foci / pathology
  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Azoxymethane / toxicity*
  • Citrus / chemistry*
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Ornithine Decarboxylase / metabolism
  • Plant Extracts / pharmacology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavonoids
  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 9
  • Ornithine Decarboxylase
  • Azoxymethane