Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon

Abstract

In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

Modulation of Pro-survival Akt/Protein Kinase B and ERK1/2 Signaling Cascades by Quercetin and Its in Vivo Metabolites Underlie Their Action on Neuronal Viability

“…The toxicity of quercetin at higher concentrations (50 M to 100 mM) toward cells in culture, in particular cancer cells, is well established and has been linked to an apoptotic mode of death (15,16,(21)(22)(23). However, little is known regarding the precise mechanism of quercetin-induced toxicity in other cell systems, and nothing is known of its effects on neurons.…”

“…Furthermore, recent evidence has shown that quercetin is extensively metabolized to O-methylated and glucuronide metabolites during absorption in the small intestine and in the liver (17,18), and such metabolites should be taken into consideration to provide in vivo relevance for any mechanism. Quercetin itself has been thoroughly investigated for its abilities to express anti-proliferative effects (19,20) and induce death predominantly by an apoptotic mechanism in cancer cell lines (21)(22)(23). For example, it has been observed to induce caspase-3 activation in the malignant cell line HPB-ALL (24), activate caspase-3 and caspase-9, release cytochrome c in HL-60 cells (25), and induce chromatin and nuclear fragmentation in colonic cancer cells (20).…”

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

“…Animal (Deschner et al, 1991;Yang et al, 2000) and in vitro studies suggest that quercetin exerts a preventive effect against cancer (Kawaii et al, 1999), but less is known about quercetin glucosides. Hollman et al (1995) show that 52% of the quercetin glucosides from onions was absorbed, whereas only 24% of free quercetin was absorbed in human model.…”

Seasonal variation in allelopathic potential of the leaves of Copaifera langsdorffii Desf.

“…As a class, fl avonoids are best known for their antioxidant activities (Bais et al 2003), but they also serve as communication signals between cell membranes, as regulators of cell growth, inducers of detoxifying enzymes, and inhibitors of seedling germination and growth (Macias et al 1997;Yang et al 2000;Hoagland & Williams 2004).…”