Prostaglandins and cancer

Abstract

Prostaglandins (PGs) are lipids produced enzymatically and nonenzymatically from 20 carbon fatty acids, particularly arachidonic acid. Prostaglandins and related metabolites (collectively referred to as eicosanoids), including the thromboxanes, prostacyclins, hydroperoxy and hydroxy fatty acids, and leukotrienes are produced by most tissues of the body by oxidation of arachidonic acid, although the amount and class of product varies with cell type. The biological action of many of these eicosanoids as key regulators of cell processes that range from proliferation to adhesion and migration are currently being elucidated. An association of high levels of PGs and their synthetic enzymes, the PG synthases/cyclooxygenases, have been noted for many of the major types of cancer. Prostaglandins may contribute to the cancer processes through one or more of several mechanisms including increased proliferation, apoptosis, enhanced carcinogen metabolism or modulation of the immune system. The recent understanding of the regulation of substrate availability and of the regulation (or dysregulation in many neoplasias) of the synthetic enzymes has opened avenues leading to the design of isozyme specific inhibitors and better cancer prevention strategies. However, the apoptosis caused by these inhibitors as well as other drugs has raised some question concerning the relative importance of PGs. This is an issue that remains to be resolved.