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

Ching Shu Lai, Mei Ling Tsai, An Chin Cheng, Shiming Li, Chih Yu Lo, Yu Wang, Hang Xiao, Chi Tang Ho, Ying Jan Wang, Min Hsiung Pan

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 6wk were injected with AOM twice weekly at a dose of 5mg/kg for 2wk and continuously fed control diet or diets containing 0.01 and 0.05% hydroxylated PMFs, respectively. Mice were then sacrificed at 6 and 20wk, 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.

Original languageEnglish
Pages (from-to)278-290
Number of pages13
JournalMolecular Nutrition and Food Research
Volume55
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

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