Potential role of P-gp for flavone-induced diminished apoptosis and increased adenoma size in the small intestine of APC(min/+) mice

Cancer Invest. 2011 Jul;29(6):396-404. doi: 10.3109/07357907.2011.587071.

Abstract

APC(min/+) mice, carrying a nonsense mutation in the adenomatous polyposis coli (APC) gene, appear as a perfect model to study development or therapy of intestinal neoplasia. We tested whether the flavonoid flavone is able to affect adenoma development in APC(min/+) mice. Tumor sizes were significantly increased by flavone selectively in small intestine. This was associated with reduced cell numbers displaying cleaved caspase-3 and enhanced expression of phosphoglycoprotein (P-gp). However, according to great variability in P-gp expression in all parts of mice intestines, an association between expression of P-gp and inhibition of apoptosis was demonstrated in human Caco-2 colorectal cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Adenoma / pathology*
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Caco-2 Cells
  • Female
  • Flavones / pharmacology*
  • Genes, APC / physiology*
  • Humans
  • Ileum / drug effects
  • Ileum / pathology
  • Intestinal Neoplasms / pathology*
  • Jejunum / drug effects
  • Jejunum / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • beta Catenin / physiology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adenomatous Polyposis Coli Protein
  • Flavones
  • beta Catenin