Potential Role of P-gp for Flavone-Induced Diminished Apoptosis and Increased Adenoma Size in the Small Intestine of APC^min/+ Mice

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.

Keywords: :

• Adenomatous polyposis coli
• Apoptosis
• Cleaved caspase
• Phosphoglycoprotein 170
• Flavone

ACKNOWLEDGMENTS

This study was supported by the Deutsche Forschungsgemeinschaft, grant number WE 2684/7–1 and 7–2. The authors greatly acknowledge Mr. Alan McDonley for critically reading the manuscript.