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Mol Nutr Food Res. 2011 Feb;55(2):278-90. doi: 10.1002/mnfr.201000224. Epub 2010 Aug 18.

Chemoprevention of colonic tumorigenesis by dietary hydroxylated polymethoxyflavones in azoxymethane-treated mice.

Author information

1
Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan.

Abstract

SCOPE:

Hydroxylated polymethoxyflavones (PMFs), existing exclusively in citrus genus, have been reported to exhibit a broad spectrum of biological activity. Here we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of hydroxylated PMFs in an azoxymethane (AOM)-induced colonic tumorigenesis model.

METHODS AND RESULTS:

Male, Institute of Cancer Research (ICR), mice at age of 6 wk were injected with AOM twice weekly at a dose of 5 mg/kg for 2 wk and continuously fed control diet or diets containing 0.01 and 0.05% hydroxylated PMFs, respectively. Mice were then sacrificed at 6 and 20 wk, and colonic tissues were collected and examined. Hydroxylated PMFs feeding dose-dependently decreased the number of aberrant crypt foci in colonic tissues of mice. More importantly, we found that hydroxylated PMFs caused a strong reduction in numbers of large aberrant crypt foci and tumors in colonic tissue. Molecular analysis exhibited the anti-proliferative, anti-inflammatory, anti-angiogenic and pro-apoptotic activities of hydroxylated PMFs by significantly decreasing the levels of inducible nitric oxide synthase, cyclooxygenase, cyclin D1 and vascular endothelial growth factor through interfering with Wnt/β-catenin and epidermal growth factor receptor/Ras/mitogen-activated protein kinase signaling pathways as well as the activation of transcription factors NF-κB and STAT3 in colonic tissue, thus resulting in suppression of colonic tumorigenesis.

CONCLUSION:

Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary hydroxylated PMFs against AOM-induced colonic tumorigenesis.

PMID:
20718052
DOI:
10.1002/mnfr.201000224
[Indexed for MEDLINE]

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