title: Quercetin Suppresses Early Colon Carcinogenesis Partly through Inhibition of Inflammatory Mediators.
abstract: We have demonstrated that 0.45% quercetin added to a diet containing corn oil (15% w/w), as the lipid source, and cellulose (6% w/w), as the fiber source, was able to suppress the formation of high multiplicity aberrant crypt foci (ACF > 4 AC/focus), to lower proliferation and enhance apoptosis in a rat model of colon cancer. This experiment determined whether quercetin was acting as an antiinflammatory molecule in an in vivo model of colon cancer. We used weanling (21 d old) Sprague Dawley rats (n = 40) in a 2×2 factorial experiment to determine the influence of quercetin on iNOS, COX-1 and COX-2 expressions, all of which are elevated in colon cancer. Half of the rats received a diet containing either 0 or 0.45% quercetin, and within each diet group, half of the rats were injected with saline or azoxymethane (AOM, 15 mg/kg BW, sc, 2× during wk 3 and 4). The colon was resected 4 wk after the last AOM injection, and the mucosa scraped and processed for RNA isolation. Data from this experiment were analyzed using a mixed model in SAS for main effects and their interaction. AOM injection stimulated (P < 0.0001) iNOS expression. However there was an interaction such that, relative to rats injected with saline, AOM-injected rats consuming diets without quercetin had significantly elevated iNOS expression (5.29-fold), but the expression in AOM-injected rats consuming the diet with quercetin was not significantly elevated (1.68-fold). COX-1 expression was 20.2% lower (P < 0.06) in rats consuming diets containing quercetin. COX-2 expression was 24.3% higher (P < 0.058) in rats consuming diets without quercetin. These data suggest inflammatory processes are elevated in this early stage of colon carcinogenesis, yet quercetin may protect against colon carcinogenesis by down-regulating the expressions of COX-1 and COX-2.
authors.affiliation: Faculty of Nutrition, Texas A&M University College Station, TX 77843-2253 USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Turner
authors.forename: K J
authors.initials: KJ
authors.lastname: Paulhill
authors.forename: C A
authors.initials: CA
authors.lastname: Warren
authors.forename: L A
authors.initials: LA
authors.lastname: Davidson
authors.forename: R S
authors.initials: RS
authors.lastname: Chapkin
authors.forename: J R
authors.initials: JR
authors.lastname: Lupton
authors.forename: R J
authors.initials: RJ
authors.lastname: Carroll
authors.forename: N
authors.initials: N
authors.lastname: Wang
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