Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells

Carcinogenesis. 1999 Mar;20(3):445-51. doi: 10.1093/carcin/20.3.445.

Abstract

We investigated whether curcumin, a chemopreventive agent, inhibited chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450, IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Curcumin also suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with CD or PMA and these effects were inhibited by curcumin. Treatment with CD or PMA increased binding of AP-1 to DNA. This effect was also blocked by curcumin. In addition to the above effects on gene expression, we found that curcumin directly inhibited the activity of COX-2. These data provide new insights into the anticancer properties of curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anticarcinogenic Agents / pharmacology
  • Chenodeoxycholic Acid / pharmacology*
  • Curcumin / pharmacology*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Digestive System / cytology
  • Digestive System / drug effects*
  • Digestive System / enzymology
  • Enzyme Induction
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / enzymology
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / genetics
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription, Genetic / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Chenodeoxycholic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Curcumin
  • Tetradecanoylphorbol Acetate