Articles
QUERCETIN SUPPRESSES EARLY COLON CARCINOGENESIS PARTLY THROUGH INHIBITION OF INFLAMMATORY MEDIATORS
Article number
841_28
Pages
237 – 242
Language
English
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 anti-inflammatory 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, 2x 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.
This experiment determined whether quercetin was acting as an anti-inflammatory 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, 2x 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.
Publication
Authors
N.D. Turner, K.J. Paulhill, C.A. Warren, L.A. Davidson, R.S. Chapkin, J.R. Lupton, R.J. Carroll, N. Wang
Keywords
iNOS, COX-1, COX-2, aberrant crypt foci
Online Articles (99)