5-Aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis

Jun Miyoshi, Tomoharu Yajima, Katsuyoshi Shimamura, Katsuyoshi Matsuoka, Susumu Okamoto, Hajime Higuchi, Shinsuke Funakoshi, Hiromasa Takaishi, Toshifumi Hibi

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4 Citations (Scopus)

Abstract

Background: Cyclooxygenase-2 (COX-2) is a key enzyme that produces prostaglandin E2 (PGE2) and plays an important role in colorectal tumor growth. In addition, recent researches focused on 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades PGE2. Here we determined the effect of 5-aminosalicylic acid (5-ASA) on COX-2 and 15-PGDH expression and investigated its preventive effect for colorectal cancer (CRC). Materials and Methods: HT-29 cells were used in the in vitro experiments. c-Ha-ras transgenic mice were employed in order to explore the chemopreventive effects. Western blotting analysis was performed and the protein expression of COX-2 and 15-PGDH was quantified. Results: 5-ASA significantly suppressed COX-2 expression and induced 15-PGDH expression in HT-29 cells. In the transgenic mice, oral 5-ASA intake reduced the incidence of colorectal tumor formation and the tumor size. Furthermore, we observed a down-regulation of COX-2 and an up-regulation of 15-PGDH in the tissue from colons of these mice. Conclusion: 5-ASA exerts a preventive effect against colorectal tumor development through mediation of COX-2 and 15-PGDH expression.

Original languageEnglish
Pages (from-to)1193-1202
Number of pages10
JournalAnticancer research
Volume32
Issue number4
Publication statusPublished - 2012 Apr 1

Keywords

  • 15-hydroxyprostaglandin dehydrogenase
  • 5-aminosalicylic acid
  • Colorectal cancer
  • Cyclooxygenase-2
  • HT-29 cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Miyoshi, J., Yajima, T., Shimamura, K., Matsuoka, K., Okamoto, S., Higuchi, H., Funakoshi, S., Takaishi, H., & Hibi, T. (2012). 5-Aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis. Anticancer research, 32(4), 1193-1202.