The nonsteroidal anti-inflammatory drug, nabumetone, differentially inhibits β-catenin signaling in the MIN mouse and azoxymethane-treated rat models of colon carcinogenesis

Hemant K. Roy, William J. Karolski, Ramesh K. Wali, Anne Ratashak, John Hart, Thomas C. Smyrk

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The mechanisms through which β-catenin signaling is inhibited during colorectal cancer chemoprevention by nonsteroidal anti-inflammatory agents is incompletely understood. We report that nabumetone decreased uninvolved intestinal mucosal β-catenin levels in the MIN mouse with a concomitant increase in glycogen synthase kinase (GSK)-3β levels, an enzyme that targets β-catenin for destruction. However, in the azoxymethane-treated rat, where β-catenin is frequently rendered GSK-3β-insensitive, nabumetone failed to alter β-catenin levels but did decrease β-catenin nuclear localization and transcriptional activity as gauged by cyclin D1. In conclusion, we demonstrate that the differential mechanisms for β-catenin suppression may be determined, at least partly, by GSK-3β.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalCancer Letters
Volume217
Issue number2
DOIs
StatePublished - Jan 20 2005

Keywords

  • Chemoprevention
  • Colon cancer
  • Nonsteroidal anti-inflammatory drugs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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