title: 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.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: Karen A
authors.initials: KA
authors.lastname: O'Leary
authors.forename: Sonia
authors.initials: S
authors.lastname: de Pascual-Teresa
authors.forename: Sonia
authors.initials: S
authors.lastname: de Pascual-Tereasa
authors.forename: Paul W
authors.initials: PW
authors.lastname: Needs
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Bao
authors.forename: Nora M
authors.initials: NM
authors.lastname: O'Brien
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D018938:Caco-2 Cells; D051546:Cyclooxygenase 2; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D007527:Isoenzymes; D008565:Membrane Proteins; D014810:Vitamin E; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases