Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in <i>Apc</i><sup>Min/+</sup> mice

  • Shimizu Satomi
    Division of Cancer Prevention Research, National Cancer Center Research Institute Faculty of Life Sciences, Toyo University
  • Fujii Gen
    Division of Cancer Prevention Research, National Cancer Center Research Institute
  • Takahashi Mami
    Central Animal Division, National Cancer Center Research Institute
  • Nakanishi Ruri
    Division of Cancer Prevention Research, National Cancer Center Research Institute
  • Komiya Masami
    Division of Cancer Prevention Research, National Cancer Center Research Institute
  • Shimura Misato
    Division of Cancer Prevention Research, National Cancer Center Research Institute School of Pharmaceutical Sciences, Tokyo University of Science
  • Noma Nobuharu
    Division of Cancer Prevention Research, National Cancer Center Research Institute School of Pharmaceutical Sciences, Tokyo University of Science
  • Onuma Wakana
    Division of Cancer Prevention Research, National Cancer Center Research Institute School of Pharmaceutical Sciences, Tokyo University of Science
  • Terasaki Masaru
    Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido
  • Yano Tomohiro
    Faculty of Life Sciences, Toyo University
  • Mutoh Michihiro
    Division of Cancer Prevention Research, National Cancer Center Research Institute

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  • Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in ApcMin/+ mice

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Abstract

Excessive prostaglandin production by cyclooxygenase-2 in stromal and epithelial cells is a causative factor of colorectal carcinogenesis. Thus, compounds which inhibit cyclooxygenase-2 transcriptional activity in colon epithelial cells could be candidates for anti-carcinogenic agents. A cyclooxygenase-2 transcriptional activity in the human colon cancer cell line DLD-1 has been measured using a β-galactosidase reporter gene system. Using this system, we demonstrated that the decrease in basal cyclooxygenase-2 transcriptional activities at 100 µM sesamol, one of the lignans in sesame seeds, was 50%. Other compounds in sesame seeds such as sesamin, sesamolin, ferulic acid, and syringic acid did not exhibit significant suppression of cyclooxygenase-2 transcriptional activity at up to 100 µM. In a following experiment, 6-week-old male Min mice, Apc-deficient mice, were divided into a non-treated and 500 ppm sesamol groups. At the age of 15 weeks, it was found that treatment with sesamol decreased the number of polyps in the middle part of small intestine to 66.1% of the untreated value. Moreover, sesamol suppressed cyclooxygenase-2 and cytosolic prostaglandin E2 synthase mRNA in the polyp parts. The present findings may demonstrate the novel anti-carcinogenetic property of sesamol, and imply that agents that can suppress cyclooxygenase-2 expression may be useful cancer chemopreventive agents.

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