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O'Leary, KA,de Pascual-Tereasa, S,Needs, PW,Bao, YP,O'Brien, NM,Williamson, G
2004
April
Effect of flavonoids and Vitamin E on cyclooxygenase-2 (COX-2) transcription
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flavonoids vitamin E cyclooxygenase quercetin NITRIC-OXIDE SYNTHASE KAPPA-B ACTIVATION COLON-CANCER CELLS INDUCIBLE CYCLOOXYGENASE MOUSE MACROPHAGES ANTIINFLAMMATORY DRUGS SODIUM-SALICYLATE ENDOTHELIAL-CELLS ARACHIDONIC-ACID EPITHELIAL-CELLS
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 un-stimulated 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 10 muM) 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. (C) 2004 Elsevier B.V. All rights reserved.
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DOI 10.1016/j.mrfmmm.2004.01.015
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