Cyclooxygenase-1 and -2 isoenzymes

The cyclooxygenase isoenzymes (COX-1 and -2) catalyze the rate-limiting ste ps in prostanoid biosynthesis. COX-1 and -2 genes encode two isoenzymes wit h overlapping yet distinct expression patterns and functions. Physiological ly, various extracellular stimuli such as growth factors, cytokines and tum or promoters regulate the expression of COX-1 and -2 genes at both transcri ptional and post-transcriptional levels. COX-2 is overexpressed in rheumato id arthritis, colorectal and breast cancer. Prostanoids produced by the COX pathway signal via plasma membrane-localized, G-protein-coupled receptors as well as via nuclear receptors, Currently, several COX-2-selective inhibi tors are developed to control the anti-inflammatory and anti-neoplastic act ivities of the COX-2 isoenzyme. Inhibition of the COX isoenzyme activity an d/or expression may be the basis of future generation of anti-inflammatory and antineoplastic drugs. (C) 1999 Published by Elsevier Science Ltd. All r ights reserved.