Effect of flavonoids and Vitamin E on cyclooxygenase-2 (COX-2) transcription

Karen A. O'Leary, Sonia De Pascual-Tereasa, Paul W. Needs, Yong Ping Bao, Nora M. O'Brien, Gary Williamson

Research output: Contribution to journalReview ArticleResearchpeer-review

310 Citations (Scopus)


Cyclooxygenase-2 (COX-2)-catalysed synthesis of prostaglandin E2 plays a key role in inflammation and its associated diseases, such as cancer and cardiovascular disease. There are numerous reports demonstrating that flavonoids inhibit COX-2 activity. However, transcriptional regulation of COX-2 can also be important. Nobiletin, amentoflavone, quercetin, quercetin penta-acetate, flavone, resveratrol, apigenin, chrysin, kaempferol, galangin, and genistein have been reported to modulate COX-2 transcription in a wide variety of systems. Here, we briefly review the literature on regulation of COX-2 transcription by flavonoids, and report some new preliminary data on Vitamin E and quercetin conjugates. Quercetin, quercetin 3-glucuronide, quercetin 3′-sulfate and 3′methylquercetin 3-glucuronide reduced COX-2 mRNA expression in both unstimulated and interleukin-1β stimulated colon cancer (Caco2) cells. Quercetin and quercetin 3′-sulfate, unlike quercetin 3-glucuronide and 3′methylquercetin 3-glucuronide, also inhibited COX-2 activity. In contrast, tocopherols (α-tocopherol, α-tocopherol acetate, and γ-tocopherol at 10 μM) did not affect COX-2 mRNA expression in unstimulated Caco2 cells. However, the tocopherols inhibited COX-2 activity showing that the tocopherols act post-transcriptionally on activity, whereas quercetin and some quercetin conjugates affect both the transcription and activity of COX-2. Flavonoid modulation of COX-2 transcription may therefore be an important mechanism in anti-carcinogenesis.

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Issue number1-2
Publication statusPublished - 13 Jul 2004
Externally publishedYes


  • Cyclooxygenase
  • Flavonoids
  • Quercetin
  • Vitamin E

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