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

Nutr Cancer. 2004;49(1):89-93. doi: 10.1207/s15327914nc4901_12.


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 1-40 microM in RAW 264.7 cells and 10-100 microM in human monocytes, isoflavones were able to reduce significantly the synthesis of prostaglandin E2 and/or thromboxane B2 (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.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Cells, Cultured
  • Cyclooxygenase 2
  • Dietary Supplements
  • Dinoprostone / biosynthesis
  • Dose-Response Relationship, Drug
  • Genistein / pharmacology
  • Humans
  • Isoflavones / pharmacology*
  • Macrophages / enzymology*
  • Membrane Proteins
  • Mice
  • Monocytes / enzymology*
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Thromboxane B2 / biosynthesis
  • Trifolium* / chemistry


  • Anticarcinogenic Agents
  • Isoflavones
  • Membrane Proteins
  • formononetin
  • Thromboxane B2
  • daidzein
  • Genistein
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • biochanin A