The Cyclooxygenase-2 Essay -- Health, Diseases

The cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins, which promote cell proliferation, angiogenesis and metastasis, and inhibit apoptosis. Unlike COX-1, which is constitutively expressed isoform, COX-2 is an inducible isoform of cyclooxygenase and which may participate in inflammatory responses and contribute to inflammation and cancersthe development of colorectal cancer as well as other human cancers (1). COX-2 is not detectable detected in most normal tissues. However, it but is rapidly induced when stimulated by in response to mitogens, cytokines and tumor promoters, which leads to the leading to increased accumulation of prostanoids in neoplastic and inflamed tissues (2). COX-2 is highly expressed at high levels in intestinal tumors in rodents and humans (1). For example, Mmore than 80% of all colorectal tumors were shown to overexpress COX-2 (3-5). Epidemiologic studies have shown that taking aspirin or other nonsteroidal anti-i nflammatory drugs on a regular basis could reduce mortality from colorectal cancer by 40-50% compared with those who not taking these drugs (1). One characteristic shared by all of these drugs is their ability to inhibit COX activity and/or expression (1). Although COX-2 is expressed in 80-90% of human colon carcinoma specimens, not all colorectal cancer cell lines constitutively expressed COX-2. Constitutive expression of COX-2 was only detected in a relatively small number of established colorectal carcinoma cell lines (6). For example, human colon adenocarcinoma cell lines, HCT116 and SW480, have been described as COX-2 negative, since they did not express COX-2, neither at mRNA nor at protein level (7). COX-2-derived prostaglandin E2 (PGE2) ... ...t as well as when the conditioned medium will be collected, with multiple parameters in which not only COX-2 mRNA and protein as well as PGE2 levels will be observed, but also other relevant molecular markers or factors like those mentioned above. Not only paradoxical observations of COX-2 expression and the functional activity in human colon cancer cell line have been documented, the role of PGE2 on inflammation seems also paradoxical. Although PGE2 is a potent mediator of inflammation (55), it was suggested that PGE2, endogenous COX products, also inhibit acute allergic inflammation (56). Thus, PGE2 may produce both pro- and anti-inflammatory effects (57). More extensive well-designed experiments are needed to help us to unveil the secret of COX-2 expression and the functional activity as well as their roles in physiological and pathophysiological conditions.