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

Abstract

BACKGROUND:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: T Kawamori, N Uchiya, T Kitamura, S Ohuchida, H Yamamoto, T Maruyama, T Sugimura, K Wakabayashi
• Journal: Anticancer research (Anticancer Res) 2001 Nov-Dec Vol. 21 Issue 6A Pg. 3865-9 ISSN: 0250-7005 [Print] Greece
• PMID: 11911260 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Bridged 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

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Azoxymethane (antagonists & inhibitors, toxicity)
• Bridged 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)