Abstract
The ability of cranberry fruit extracts to inhibit colon carcinogenesis was investigated using a combination of in vitro and in vivo methods. Compounds isolated from cranberry fruit (Vaccinium macrocarpon) were shown to decrease the rate of cell proliferation as well as the percentage of viable HCT116 and HT-29 colon cancer cells while lesser effects were observed with CCD-18Co normal cells. Based on cranberry's effect in vitro, a feeding study was conducted by collaborators in the Department of Food Science at University of Massachusetts Amherstusing Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) mice, an inflammatory colon cancer model that mimics colitis. Mice were treated with AOM and DSS to induce inflammation-driven colon carcinogenesis, while receiving an AIN-93 diet containing whole cranberry powder, concentrated polar polyphenolic extract, nonpolar extract or no cranberry (control). Not only was the number and size of tumors decreased in the cranberry treated mice, but inflammation markers were decreased. It has been shown that inflammation is linked to the growth of colon cancer in vivo. With this knowledge, the effect of specific cranberry isolates on production ofInterleukin-6 (IL- 6), a cytokine marker of inflammation, was determined in vitro using an enzyme-linked immunosorbent assay. Colon cells were stimulated with phorbolmyristate acetate to initiate an inflammatory response then treated with several difference cranberry fruit extracts before IL-6 was measured. The cranberry extracts, specifically Quercetin, a flavonol, significantly decreased the amount of IL-6 in the colon cells. Metabolic profiling through Ultra Performance Liquid Chromatography with Mass Spectrometry was also used as a tool to determine how the composition of mouse colon metabolites was affected by the cranberry dietary treatments. Several possible polyphenol metabolites were identified in the fecal extracts of the cranberry-fed mice. Epigallocatechin 3-O-gallate and resveratrol were two of the more well-known compounds identified. These studies demonstrate potential for dietary cranberry constituents and metabolites to inhibit colon carcinogenesis through decreased inflammation.