Cyclooxygenase expression is not required for release of arachidonic acid from cells by some nonsteroidal anti-inflammatory drugs and cancer preventive agents.
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


CONCLUSIONS
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.
Levine
Lawrence
L
Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA. llevine@brandeis.edu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases