Development and use of a gene promoter-based screen to identify novel inhibitors of cyclooxygenase-2 transcription Academic Article Article uri icon


MeSH Major

  • Adiponectin
  • Adipose Tissue, White
  • Aromatase
  • Breast
  • C-Reactive Protein
  • Interleukin-6
  • Leptin
  • Menopause


  • Cyclooxygenase-2 (COX-2) is a recognized target for cancer prevention and possibly treatment. To identify novel inhibitors of COX-2, we developed a high throughput reporter gene assay that utilizes a region of the human COX-2 promoter to drive luciferase expression. A total of 968 extracts from 266 plants were screened. Extracts from 12 plants (4.5%), including Arnebia euchroma, a medicinal plant used in the Far East to treat inflammation, inhibited the stimulation of COX-2 promoter activity. The gene promoter assay then was used to identify shikonin, a compound with known anti-inflammatory and chemopreventive properties, as an active compound in A. euchroma. To complement the gene promoter studies, we determined the effects of a mixture of shikonins on phorbol 12-myristate 13-acetate (PMA)-mediated induction of COX-2 in transformed human mammary epithelial cells. Shikonins inhibited PMA-mediated induction of COX-2 mRNA, protein, and prostaglandin E(2) synthesis. In transient transfections, PMA caused a severalfold increase in COX-2 promoter activity, an effect that was suppressed by shikonins. Shikonins also inhibited PMA-mediated stimulation of extracellular signal-regulated kinase1/2 mitogen-activated protein kinases and activator protein-1 activity. Collectively, these results demonstrate the successful development and use of a high throughput reporter gene assay for the identification of a novel inhibitor of COX-2 expression.

publication date

  • May 7, 2001



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1089/108705701750160282

PubMed ID

  • 11689104

Additional Document Info

start page

  • 101

end page

  • 10


  • 6


  • 2