© 1998 by Oxford University Press
Journal of the National Cancer Institute, Vol. 90, No. 20, 1529-1536,
October 21, 1998
©Copyright 1998 Oxford University Press
REVIEW |
Cyclooxygenase-2 Inhibitors in Tumorigenesis (Part I)
Affiliation of author: Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Correspondence to: Makoto M. Taketo, M.D., Ph.D., Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113, Japan (e-mail:taketo{at}mol.f.u-tokyo.ac.jp).
Dedicated to Sir Professor John Vane and Professor Osamu Hayaishi whose works inspired me to enter into this fascinating field of research.
The rate-limiting enzyme in arachidonate metabolism is mediated by enzymes known as cyclooxygenases (COXs). These enzymes catalyze the biosynthesis of prostaglandin H2, the precursor of molecules, such as prostaglandins, prostacyclin, and thromboxanes. The COX enzyme family consists of the classical COX-1 enzyme, which is constitutively expressed in many tissues, and a second enzyme, i.e., COX-2, which is induced by various stimuli, such as mitogens and cytokines, and is involved in many inflammatory reactions. Because nonsteroidal anti-inflammatory drugs inhibit both COX-1 and COX-2, these drugs also cause unwanted side effects, exemplified by gastrointestinal bleeding. Accumulating evidence indicates that nonsteroidal anti-inflammatory drugs can reduce the incidence of colorectal cancers in human and experimental animals and can reduce the polyp number and size in patients with familial adenomatous polyposis. This Part I (of a two-part review) focuses on the discovery of the COXs; their biochemical, molecular, and structural properties; and on the discovery of isozyme-specific inhibitors of COX activity. [J Natl Cancer Inst 1998;90:1529-36]
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