Aldose reductase regulates TNF-α-induced PGE2 production in human colon cancer cells

Ravinder Tammali, Kota Ramana, Satish Srivastava

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Pro-inflammatory cytokines such as TNF-α play an important role in the pathophysiology of diseases such as Crohn's and ulcerative colitis which cause increased risk of colorectal cancer. However, the mechanisms underlying colon carcinogenesis are not well understood. Herein we report that inhibition/antisense abolition of polyol pathway enzyme, aldose reductase (AR) inhibited the TNF-α-induced synthesis of prostaglandin E2 and the activity of cyclooxygenase (Cox) in human colon cancer cells, Caco-2. Inhibition of AR prevented TNF-α-induced activation of PKC and NF-κB which resulted in the abrogation of Cox-2 mRNA and protein expression. These results suggest that inhibition of AR could be a novel chemopreventive approach to colon cancer.

Original languageEnglish (US)
Pages (from-to)299-306
Number of pages8
JournalCancer Letters
Volume252
Issue number2
DOIs
StatePublished - Jul 18 2007

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Keywords

  • Aldose reductase
  • Colon cancer
  • Inflammation
  • NF-κB
  • PGE2
  • PKC
  • TNF-α

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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