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

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.