Cyclooxygenase (COX)-2 and COX-1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which is crucial in cholesterol biosynthesis. Recently, cholesterol-independent effects of statins have been described. In this study, we evaluated the effect of two...

Targeting the prostaglandin (PG) pathway is potentially a critical intervention for the prevention and treatment of cancer. Central to PG biosynthesis are two isoforms of cyclooxygenase (COX 1 and 2), which produce prostaglandin H(2) (PGH(2)) from plasma membrane stores of fatty acids. COX-1 is constitutively expressed, whereas COX-2 is an inducible isoform upregulated in many cancers. Differen...

Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development and also clarify the underlying mechanisms. Data clearly showed that COX-1 was ...

BACKGROUND Drugs that inhibit cyclooxygenase-2 (COX-2) while sparing cyclooxygenase-1 (COX-1) represent a new attractive therapeutic development and offer new perspective for further use of COX-2 inhibitors. Intention of this work is to develop safer, selective COX-2 inhibitors that do not produce harmful effects. RESULTS A series of 55 tyrosine derivatives were designed for evaluation as sel...

Cyclooxygenase (COX)-2 and COX-1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which is crucial in cholesterol biosynthesis. Recently, cholesterol-independent effects of statins have been described. In this study, we evaluated the effect of two...

Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostaglandin H2. The inducible isoform, COX-2, promotes colorectal tumorigenesis, and nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit this isoform are chemopreventive in murine models of intestinal tumorigenesis. To establish a mechanism for their chemopreventive properties, we examined the effect of a ...

In 1971, Vane showed that the analgesic action of traditional NSAIDs relies on inhibition of the cyclo-oxygenase (COX) enzyme, which in turn results in reduced synthesis of proalgesic prostaglandins. Two decades later COX was shown to exist as two distinct isoforms. The constitutive isoform COX-1, supports the beneficial homeostatic functions whereas the inducible isoform, COX-2 becomes up regu...

Selective cyclooxygenase-2 (COX-2) inhibitors were developed to reduce the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents. However, COX-2 inhibitors decrease prostacyclin production and may disrupt the normal homeostatic balance, leading to a prothrombotic state and offsetting the potential gastrointestinal benefits. Available clinical data and basic biological ...

Hyaluronan (HA) is a key molecule of the extracellular matrix that is thought to be critically involved in both atherosclerosis and restenosis. Recently, it has been demonstrated that the cyclooxygenase (COX) products, prostacyclin and prostaglandin E(2), induce HA synthesis in vitro by transcriptional up-regulation of HA-synthase 2 (HAS2) and HAS1. The relative roles in atherosclerotic and res...

Selective inhibitors of cyclooxygenase-2 (COX-2, 'coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non-steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myo cardial inf...