Colorectal cancer remains one of the most common causes of cancer mortality in Western society and currently has a five year survival rate of 50% (Boyle and Ferlay, 2004). Therefore alternative strategies are needed to alleviate the burden being placed in the health-care system. An attractive solution is chemoprevention. Over the last decade there have been a number of natural and synthetic compounds which have been found to have chemopreventative properties, such as non-steroidal anti-inflammatory drugs (NSAIDs) and natural compounds such as flavonoids and curcumin. Ellagitannins are compounds which are found in abundance in many foods but in particular in soft fruits and are naturally metabolised to ellagic acid (EA). The mechanism of action of these compounds is still unclear, however it is possible that they may work through the inhibition of a general cell growth pathway and we hypothesise that the polyamine biosynthesis may be the pathway involved. Polyamines are natural polycations which are found in almost all cells and at increased concentrations in cancer cells and tissues (Kingsnorth et al 1984). The metabolism of the polyamines is tightly regulated and the key rate-limiting enzyme is ornithine decarboxylase (ODC). The aims of this study were to (i) determine and compare the cytotoxicity of NSAIDs and EA in a range of colorectal cancer cell lines and (ii) to establish the extent of involvement of polyamine metabolism in the cytotoxic process. Using 4 colorectal cancer cell lines we established the cytotoxicity of the NSAIDs and EA using MTT (Fig. 1), Trypan Blue exclusion and protein determination were used to monitor cell growth. Polyamine analysis was carried out by HPLC. Aspirin and EA exposure resulted in dose-dependent cytotoxicity. IC50 values were calculated from MTT assays (Fig.1) of 5.5 mM for aspirin and 75 μg/ml for EA. Cell number, viability and protein content decreased with increasing exposure (results not shown). Analysis of polyamine concentrations showed that the total intracellular polyamine content decreased after exposure to these compounds. There was inhibition of ODC activity and that there was an increase in the catabolism of polyamines, at least in the presence of the NSAIDs. Thus, it seems that, at least, part of the mechanism of cytotoxicity of these compounds is modulation of the polyamine pathway.