Abstract

Colorectal cancer (CRC) is the fourth leading cause of tumor-related deaths worldwide. In this study, we explored the in vivo effects of quercetin, a plant flavonol from the flavonoid group of polyphenols with antioxidant effects, on colon carcinogenesis induced by azoxymethane/dextran sodium sulfate (AOM/DSS). Thirty mice were randomly assigned into three groups: the control group, the AOM/DSS group, and the quercetin+AOM/DSS group. CRC was induced by AOM injection and a solution of 2% DSS in the drinking water. In the AOM/DSS-induced colon cancer mice model, quercetin treatment dramatically reduced the number and size of colon tumors. In addition, quercetin significantly restored the leukocyte counts by decreasing the inflammation caused by AOM/DSS. We also observed that the expression of oxidative stress markers, such as lipid peroxide (LPO), nitric oxide (NO), superoxide dismutase (SOD), glucose-6-phosphate (G6PD), and glutathione (GSH), could be reduced by quercetin, suggesting that the anti-inflammatory function of quercetin comes from its antioxidant effect. Moreover, potential biomarkers were identified with serum metabolite profiling. Increased levels of 2-hydroxybutyrate, 2-aminobutyrate, and 2-oxobutyrate and decreased levels of gentian violet, indole-3-methyl acetate, N-acetyl-5-hydroxytryptamine, indoxyl sulfate, and indoxyl were also found in the AOM/DSS-treated mice. However, quercetin treatment successfully decreased the levels of 2-hydroxybutyrate, 2-aminobutyrate, 2-oxobutyrate, endocannabinoids, and sphinganine and increased the levels of gentian violet, N-acetyl-5-hydroxytryptamine, indoxyl sulfate, and indoxyl. Together, our data demonstrated that quercetin could maintain relatively potent antitumor activities against colorectal cancer in vivo through its anti-inflammation effect.

Highlights

  • Colon carcinoma is one of the most common malignant tumors observed in clinical practice [1]

  • Feeding mice with azoxymethane/dextran sodium sulfate (AOM/DSS) alone or AOM/DSS together with quercetin did not produce any statistically significant colon length changes when compared to the control mice (Figure 2)

  • These observations indicated that quercetin could reverse AOM/DSS-induced colon carcinogenesis in mice

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Summary

Introduction

Colon carcinoma is one of the most common malignant tumors observed in clinical practice [1]. Emerging evidence confirms that there is a marked survival difference among CRC patients that is largely due to the tumor stage at the time of diagnosis For this reason, effective treatments for CRC are still needed. The AOM/DSS-induced mouse model of CAC is one of the most widely used chemically induced CRC models due to its high reproducibility and potency Studies based on this model have demonstrated the importance of the inflammation process in CRC development and have elucidated some of the mechanisms of inflammation-related colon carcinogenesis in the gut, with an emphasis on the function of pro- and anti-inflammatory cytokines [8, 10]. Whether or not quercetin can suppress the proliferation characteristics of colon cancer cells needs further investigation For these reasons, in this study, we explored the in vivo effects of quercetin on AOM/DSS-induced colon carcinogenesis. We evaluated the colon carcinogenesis, oxidative stress, and potential serum biomarkers in different groups of mice

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