Nonsteroidal anti-inflammatory drugs stimulate spermidine/spermine acetyltransferase and deplete polyamine content in colon cancer cells

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit colonic tu mourigenesis and have an established usefulness in cancer prevention. Becau se polyamines are essential for neoplastic cell growth, the aim of this stu dy was to evaluate the effect of NSAIDs (indomethacin, a nonselective COX-1 and COX-2 inhibitor) on polyamine metabolism in colon cancer cells. Methods Both cell counting and thymidine incorporation into cellular DNA we re used to assess colon cancer cell growth. Activities of polyamine-metabol ising enzymes, polyamine content (HPLC) and ODC and c-myc protein expressio n (Western blot) were measured in colon cancer cells treated with indometha cin during logarithmic phase of proliferation. Results Indomethacin impaired growth of human colon cancer cells (Caco-2 an d HCT-116). As a result, ornithine decarboxylase activity and c-myc protein expression were decreased. Treatment with indomethacin induced intracellul ar oxidant formation in colon cancer cells significantly increased the sper midine/spermine-acetyltrasferase activity (SSAT) and enhanced polyamine ace tylation and efflux from colon cancer cells. Impairment of cell growth by i ndomethacin could not be reversed by exogenous polyamines. Conclusions Taken together, our results suggest that NSAIDs affect polyamin e metabolism in colon cancer cells by inducing SSAT activity, and that poly amine depletion in NSAID-treated colon cancer cells is mainly due to enhanc ed polyamine acetylation and irreversible depletion of intracellular polyam ine pools.