Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling

PLoS One. 2011;6(8):e22934. doi: 10.1371/journal.pone.0022934. Epub 2011 Aug 8.


Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Antioxidants / pharmacology
  • Blotting, Western
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • NF-kappa B / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Oligonucleotide Probes / genetics
  • Oligonucleotide Probes / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Purines / pharmacology
  • Quercetin / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Roscovitine
  • Signal Transduction / drug effects*
  • p300-CBP Transcription Factors / antagonists & inhibitors
  • p300-CBP Transcription Factors / metabolism*


  • Antioxidants
  • CCAAT-Enhancer-Binding Protein-beta
  • NF-kappa B
  • Oligonucleotide Probes
  • Purines
  • Roscovitine
  • Quercetin
  • Cyclooxygenase 2
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Dinoprostone