Effect of red clover isoflavones on COX-2 activity in murine and human monocyte/macrophage cells

Long-term use of nonsteroidal anti-inflammatory drugs is associated with a reduction in the incidence of a range of cancers, the mechanism of which is thought to be cyclooxygenase (COX) inhibition. Because long-term ingestion of foods rich in isoflavones, such as legumes (beans, peas, lentils) has been associated with reduced cancer incidence, it was considered useful to examine the COX-inhibitory activities of individual isoflavones. Red clover dietary supplements also contain varying ratios of the 4 isoflavones commonly found in legume-based diets, namely, daidzein, genistein, formononetin, and biochanin. Using 2 separate cell assays, this study examined the ability of the isoflavones found in red clover to inhibit COX enzyme activity in both the murine macrophage cell line RAW 264.7 and human monocytes. Within the range of 1-40muM in RAW 264.7 cells and 10-100muM in human monocytes, isoflavones were able to reduce significantly the synthesis of prostaglandin E-2 and/or thromboxane B-2 (P < 0.001 to P < 0.05), indicating COX inhibition. Thus, it is possible that the lower rates of some cancers in populations with a high intake of dietary isoflavones is linked to their inhibition of COX activity.