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-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.