Abstract
Abstract
Background
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in inhibiting colorectal cancer. Cyclooxygenase activity is thought to mediate, in part, this cancer preventive effect. From observations made when cells that express cyclooxygenase activity were treated with NSAIDs and known cancer preventive agents, I have postulated that arachidonic acid (AA) release is associated with cancer prevention. In this study, the effects of NSAIDs on two cells that do not express cycloxygenase activity are detailed.
Results
NSAIDs and several cancer preventive agents release AA from human colon cancer cells (the HCT-15 cell line). The concentrations of NSAIDs required to release significant amounts of AA from the HCT-15 cells are greater than those required to inhibit the lactacystin plus 12-0-tetradecanoyl-13-acetate stimulated cyclooxygenase activity of rat liver cells. NSAIDs, tamoxifen and simvastatin were found to hemolyze erythrocyte cells which also do not express cyclooxygenase activity
Conclusion
The data demonstrate that AA release is independent of cyclooxygenase activity and together with hemolysis suggest that intercalation of the plasma membrane by some NSAIDs and cancer preventive agents, e.g. tamoxifen, mediates this release. A mechanism by which many of these drugs affect several diverse biologic properties including deesterification of membrane phospholipids by phospholipases to release AA is presented.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology
Reference35 articles.
1. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971, 231: 232-235.
2. Abramson SB, Weissmann G: The mechanisms of action of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1989, 32: 1-9.
3. Weissmann G: Aspirin. Sci Am. 1991, 264: 84-90.
4. Kune GA, Kune S, Watson LF: Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res. 1988, 48: 4399-4404.
5. Tashjian AH, Voelkel EF, Goldhaber P, Levine L: Successful treatment of hypercalcemia by indomethacin in mice bearing a prostaglandin-producing fibrosarcoma. Prostaglandins. 1973, 3: 515-524. 10.1016/0090-6980(73)90161-5.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献