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

Abstract

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-1beta 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 (alpha-tocopherol, alpha-tocopherol acetate, and gamma-tocopherol at 10microM) 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.

• Authors: Karen A O'Leary, Sonia de Pascual-Teresa, Sonia de Pascual-Tereasa, Paul W Needs, Yong-Ping Bao, Nora M O'Brien, Gary Williamson
• Journal: Mutation research (Mutat Res) Vol. 551 Issue 1-2 Pg. 245-54 (Jul 13 2004) ISSN: 0027-5107 [Print] Netherlands
• PMID: 15225597 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Flavonoids
• Isoenzymes
• Membrane Proteins
• Vitamin E
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Antioxidants (pharmacology)
• Caco-2 Cells
• Cyclooxygenase 2
• Flavonoids (pharmacology)
• Humans
• Isoenzymes (genetics)
• Membrane Proteins
• Prostaglandin-Endoperoxide Synthases (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription, Genetic
• Vitamin E (pharmacology)