Anti-cancer Effects of MW-03, a Novel Indole Compound, by Inducing 15-Hydroxyprostaglandin Dehydrogenase and Cellular Growth Inhibition in the LS174T Human Colon Cancer Cell Line

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  • Seira Naofumi
    Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Yanagisawa Naoki
    Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Suganami Akiko
    Department of Bioinformatics, Graduate School of Medicine, Chiba University
  • Honda Takuya
    Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Wasai Makiko
    Department of Chemistry, Graduate School of Science, Chiba University
  • Regan John W.
    Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona
  • Fukushima Keijo
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences & Graduate School of Biomedical Sciences, Tokushima University
  • Yamaguchi Naoto
    Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Tamura Yutaka
    Department of Bioinformatics, Graduate School of Medicine, Chiba University
  • Arai Takayoshi
    Department of Chemistry, Graduate School of Science, Chiba University
  • Murayama Toshihiko
    Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Fujino Hiromichi
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences & Graduate School of Biomedical Sciences, Tokushima University

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<p>Increases in the expression of prostaglandin E2 (PGE2) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase. Although the target of MW-03 for cell cycle inhibition has not yet been identified, these dual anti-cancer effects of MW-03 itself and/or its leading compound(s) on colon cancer cells may reduce colon cancer development and, thus, have potential as a novel treatment for the early stage of this disease.</p>

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