Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription.
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.
O'Leary
Karen A
KA
Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
de Pascual-Teresa
Sonia
S
de Pascual-Tereasa
Sonia
S
Needs
Paul W
PW
Bao
Yong-Ping
YP
O'Brien
Nora M
NM
Williamson
Gary
G
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*
D000975:Antioxidants; D005419:Flavonoids; D007527:Isoenzymes; D008565:Membrane Proteins; D014810:Vitamin E; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases