Evaluation of a selective prostaglandin E receptor EP1 antagonist for potential properties in colon carcinogenesis.

Cyclooxygenases (COXs) and prostanoids play pivotal roles in colon carcinogenesis. This study was designed to determine the chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and to compare its potential with that of nimesulide, a well-documented selective COX-2 inhibitor.
Five-week-old male F344 rats received s.c. injections of AOM (15 mg/kg body weight) or the saline vehicle once weekly for two weeks and were fed the control diet (AIN-76A) or the experimental diets containing 400 or 800 ppm of ONO-8711 or 400 ppm nimesulide for 5 weeks.
Administration of ONO-8711 at 800 ppm significantly reduced the total number of ACF/colon and 5-bromodeoxyuridine (BrdUrd) labeling index as compared to the control diet group (by 31% and 66%, respectively). As expected, dietary administration of nimesulide also suppressed the development of ACF and BrdUrd labeling index in the colon, by about 39% and 54%, respectively.
Our finding that ONO-8711 significantly suppresses colonic ACF formation and cell proliferation strengthens the hypothesis that the selective prostaglandin E receptor EP1 antagonists possesses chemopreventive activity against colon cancer development.
AuthorsT Kawamori, N Uchiya, T Kitamura, S Ohuchida, H Yamamoto, T Maruyama, T Sugimura, K Wakabayashi
JournalAnticancer research (Anticancer Res) 2001 Nov-Dec Vol. 21 Issue 6A Pg. 3865-9 ISSN: 0250-7005 [Print] Greece
PMID11911260 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticarcinogenic Agents
  • Bicyclo Compounds
  • Caproates
  • Carcinogens
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • ONO 8711
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype
  • Sulfonamides
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Azoxymethane
  • nimesulide
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Azoxymethane (antagonists & inhibitors, toxicity)
  • Bicyclo Compounds (pharmacology)
  • Caproates (pharmacology)
  • Carcinogens (antagonists & inhibitors, toxicity)
  • Cell Division (drug effects)
  • Colonic Neoplasms (chemically induced, pathology, prevention & control)
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors (pharmacology)
  • DNA Fragmentation (drug effects)
  • Isoenzymes (antagonists & inhibitors)
  • Male
  • Precancerous Conditions (chemically induced, pathology, prevention & control)
  • Prostaglandin-Endoperoxide Synthases
  • Rats
  • Rats, Inbred F344
  • Receptors, Prostaglandin E (antagonists & inhibitors)
  • Receptors, Prostaglandin E, EP1 Subtype
  • Sulfonamides (pharmacology)

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