Epidemiological studies indicate that Asian women have a lower incidence of breast cancer compared with their counterparts in the West, and soya consumption has been suggested as a contributory factor. Clinical and animal studies have revealed that cyclooxygenase-2 (COX-2) expression is associated with a risk of breast cancer. In the present study, we investigated the effect of soya isoflavones on the expression of COX-2 in the breast cell line MCF-7. Genistein, daidzein and equol were found to inhibit COX-2 expression induced by phorbol 12-myristate 13-acetate (PMA). Similar findings were observed in the COX-2 protein analysis. In order to study transcriptional control, a fragment of the 5′-flanking region of the hCOX-2 gene was amplified and inserted into a firefly luciferase reporter plasmid. The reporter assay indicated that the transactivation of the hCOX-2 promoter was induced by PMA, and activity was inhibited with the co-administration of genistein, daidzein or equol. An activator protein-1 (AP-1)/cyclic AMP response element binding protein (CREB) binding site (−59/−53) was identified in hCOX-2 promoter, and this could be critical in PMA-induced COX-2 expression. Truncation reporter plasmids with (−70/−36) and without (−51/−36) AP-1/CREB were constructed for subsequent analysis. The results revealed that the hCOX-2 promoter transactivation suppressed by isoflavone could be dependent on AP-1/CREB binding. Nonetheless, this study illustrated that the soya isoflavones reduced COX-2 expression, which could be important in the post-initiation events of breast carcinogenesis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. However, their long-term use is limited by gastrointestinal (GI) side effects such as gastric ulcers. NSAIDs act by inhibiting an enzyme called cyclooxygenase. Cyclooxygenase (COX) catalyses the generation of prostaglandins from arachidonic acid. Two isoforms of the enzyme exist – COX-1 and COX-2 – both of which are targets for NSAIDs. Although they are associated with GI toxicity, NSAIDs have important antithrombotic and anti-inflammatory effects. The GI injury has been attributed to COX-1 inhibition and the anti-inflammatory effects to COX-2 inhibition. As COX-2 is traditionally viewed as an inducible enzyme, selective inhibition of COX-2 by ‘coxibs’ (selective COX-2 inhibitors) has been employed to achieve anti-inflammatory and analgesic effects without GI side effects. However, recently there have been suggestions that chronic administration of coxibs might increase the risk of cardiovascular events, such as atherosclerosis, compared with traditional NSAIDs. In vascular disease, there is increased expression of both COX-1 and COX-2, resulting in enhanced prostaglandin generation. The specific role of COX-1 and COX-2 in vascular regulation is still unknown but such knowledge is essential for the effective use of coxibs. Although more evidence is pointing to selective COX-1 inhibition as a therapeutic measure in inflammatory atherosclerosis, there are some studies that suggest that inhibition of COX-2 might have a potential benefit on atherosclerosis.