Journal
BIOCHEMICAL JOURNAL
Volume 374, Issue -, Pages 481-488Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20030280
Keywords
apoptosis; colorectal cancer; chemoprevention; non-steroidal anti-inflammatory drug; polyamine; spermidine; spermine
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Naproxen, sulindac and salicylate, three NSAIDs (nonsteroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content. Inhibition of ornithine decarboxylase (the first enzyme of the polyamine biosynthetic pathway), induction of polyamine oxidase and spermidine/spermine N'-acetyltransferase (the enzymes responsible for polyamine catabolism) and induction of polyamine export all contributed to the decreased intracellular polyamine content. Morphological examination of the cells showed typical signs of apophosis, and this was confirmed by DNA fragmentation and measurement of caspase-3-like activity. Re-addition of spermidine to the cells partially prevented apoptosis and recovered the cell number. Thus polyamines appear to be an integral part of the signalling pathway mediating NSAID toxicity in human colorectal cancer cells, and may therefore also be important in cancer chemoprevention in humans.
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