Does the release of arachidonic acid from cells play a role in cancer chemoprevention?

COX-2 is overexpressed in cancer cells and has become a major target for cancer preventive drugs. NSAIDs, retinoids, antioxidants, and PPAR agonists, reported to be chemopreventive, suppress COX-2 synthesis. NSAIDs also have been shown to be chemopreventive independent of COX-2 activity. Common to all of these compounds is their ability to release arachidonic acid (AA) from rat liver cells in culture. Most of these compounds inhibit induced PGI2 production. Vitamin D3 and tamoxifen, however, not only stimulate the release of AA from cells: they amplify rather than inhibits induced COX activity. In view of the many activities attributable to AA, I propose that its release and accumulation could initiate molecular reactions that lead to apoptosis and eventually to suppression of cancer. Some drugs shown to release AA from cells and affect PGI2 production-e.g., thiazolidinediones and statins are widely used for conditions unrelated to cancer. In vivo studies could reveal whether they can also function as cancer preventive agents.