Sodium salicylate and 5-aminosalicylic acid synergistically inhibit the growth of human colon cancer cells and mouse intestinal polyp-derived cells

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  • Takakura Hideki
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hiroshima International University
  • Horinaka Mano
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine
  • Imai Ayaka
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine
  • Aono Yuichi
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Department of Biomedical Chemistry, Kwansei Gakuin University
  • Nakao Toshimasa
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine
  • Miyamoto Shingo
    Epidemiology and Prevention Division, Center for Public Health Sciences, National Cancer Center
  • Iizumi Yosuke
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine
  • Watanabe Motoki
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine
  • Narita Takumi
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine
  • Ishikawa Hideki
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine
  • Mutoh Michihiro
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Epidemiology and Prevention Division, Center for Public Health Sciences, National Cancer Center
  • Sakai Toshiyuki
    Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine

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Abstract

<p>As colon cancer is one of the most common cancers in the world, practical prevention strategies for colon cancer are needed. Recently, treatment with aspirin and/or 5-aminosalicylic acid-related agents was reported to reduce the number of intestinal polyps in patients with familial adenomatous polyposis. To evaluate the mechanism of aspirin and 5-aminosalicylic acid for suppressing the colon polyp growth, single and combined effects of 5-aminosalicylic acid and sodium salicylate (metabolite of aspirin) were tested in the two human colon cancer cells with different cyclooxygenase-2 expression levels and intestinal polyp-derived cells from familial adenomatous polyposis model mouse. The combination induced cell-cycle arrest at the G1 phase along with inhibition of cell growth and colony-forming ability in these cells. The combination reduced cyclin D1 via proteasomal degra­dation and activated retinoblastoma protein. The combination inhibited the colony-forming ability of mouse colonic mucosa cells by about 50% and the colony-forming ability of mouse intestinal polyp-derived cells by about 90%. The expression level of cyclin D1 in colon mucosa cells was lower than that in intestinal polyp-derived cells. These results suggest that this combination may be more effective in inhibiting cell growth of intestinal polyps through cyclin D1 down-regulation.</p>

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