PubMed · 8959921
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D Golding. 1996. Managing gout in practice.. https://pubmed.ncbi.nlm.nih.gov/8959921/
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Nonsteroidal antiinflammatory drugs (NSAIDs) can inhibit colorectal tumorigenesis and are among the few agents known to be useful for the chemoprevention of neoplasia. Here, we show that the tumor suppressive effects of NSAIDs are not likely to be related to a reduction in prostaglandins but rather are due to the elevation of the prostaglandin precursor arachidonic acid (AA). NSAID treatment of colon tumor cells results in a dramatic increase in AA that in turn stimulates the conversion of sphingomyelin to ceramide, a known mediator of apoptosis. These results have significant implications for understanding and improving colon cancer chemoprevention.
A displacement equation describing competitive binding of drugs to protein in solution is derived and examined with four nonsteroidal anti-inflammatory drugs and human serum albumin as model drugs and protein, respectively. Microdialysis/high-performance liquid chromatography was adopted to determine simultaneously the unbound solute and displacing agent in drug-protein solutions. The method is able to locate the binding site and determine affinity constants even up to 10(7) L/mol accurately. A comparison of association constants determined by this method and from capacity factors on HSA-CSP is given.