Arachidonic Acid Cascade Enzyme Inhibition and Cancer

J.   J.   Moreno

Abstract

Arachidonic acid (AA) metabolites are lipid signalling mediators that play a central role in a broad array of physiological and pathophysiological processes, including cell proliferation and differentiation. AA metabolism diverges into two main pathways, the cyclooxygenase (COX) pathway, which leads to prostaglandin and thromboxane production, and the lipoxygenase (LOX) pathway, which leads to the leukotriene and hydroxyeicosatetraenoic acid production. These inflammatory molecules exert profound biological effects that enhance the development and progression of human cancers. A large number of synthetic drugs and natural molecules inhibit the enzymes involved in these pathways and thus prevent, delay or reverse inflammation. They may also prove useful in the chemoprevention of cancer. These studies have primarily used non-steroidal anti-inflammatory drugs, which block the COX pathway. Recent pre-clinical studies indicate that the LOX pathway is also a key target for cancer prevention strategy. This article reviews the role of COX and LOX inhibitors in cell proliferation and cancer.

Keywords: prostaglandins, leukotrienes, eicosanoids, cyclooxygenase, lipoxygenase, cell proliferation, cell growth, neoplasia