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Comment
. 1999 Aug 16;190(4):445-50.
doi: 10.1084/jem.190.4.445.

The role of cyclooxygenase inhibition in the antineoplastic effects of nonsteroidal antiinflammatory drugs (NSAIDs)

S J Shiff  1 , B Rigas
Affiliations
Comment

The role of cyclooxygenase inhibition in the antineoplastic effects of nonsteroidal antiinflammatory drugs (NSAIDs)

S J Shiff et al. J Exp Med. .
No abstract available

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Figures

Figure 1
Figure 1
Colorectal carcinogenesis. Normal epithelial cells acquire abnormal growth and morphological characteristics and form an aberrant crypt focus, which enlarges to become an adenoma. With time, adenomas increase in size and can become adenocarcinomas, which have the ability to invade and metastasize. Presumably driving this process are somatic mutations that develop in the designated key genes in the colonocytes that make up these lesions; abnormalities in DNA mismatch repair mechanisms can also contribute. Aspirin and other NSAIDs inhibit this process, perhaps at several distinct points. Figure is adapted from reference 2.
Figure 2
Figure 2
Arachidonic acid metabolism by COX isoenzymes. Phospholipase A2 (PLA2) releases arachidonic acid (AA) from membrane phospholipids, which is in turn converted by either COX-1 or COX-2 to PGG2 (C, cyclooxygenase catalytic activity of COX) and then to PGH2 (P, peroxidase catalytic activity of COX). PGH2 is converted to either PGs (e.g., E2, F2α, I2, D2); thromboxane A2 (TxA2); or malondialdehyde (MDA). MDA is a direct-acting mutagen and carcinogen and can be produced without COX by direct lipid peroxidation. AA can be converted directly to 15-(R)-HETE by both COX isoenzymes. COX-1 is constitutively expressed in most tissues, whereas COX-2 is induced by cytokines, growth factors, tumor promoters, or other agents after the initiation of specific physiological events. Compounds other than PGG2, e.g., procarcinogenic hydroperoxides, can serve as substrates for the peroxidase activity of both COX enzymes. Inactive carcinogens serving as electron acceptors can also become activated by this activity. The COX isoenzymes are also involved in the formation of peroxyl radicals that can activate procarcinogens. Figure is adapted from reference 3.
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