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Resveratrol is a naturally occurring polyphenol with cancer chemopreventive properties in preclinical models of carcinogenesis, including those of colorectal cancer. Recently DMU212, an analogue of resveratrol, was found to be superior to resveratrol in terms of growth-inhibitory and pro-apoptotic properties in transformed cells, when compared with their untransformed counterparts (Lu J. et al., Carcinogenesis, 22: 321-328, 2001). We wished to compare the ability of resveratrol and DMU212 to prevent malignancies associated with Apc mutations. To that end ApcMin/+ mice received resveratrol or DMU212 admixed in the diet at 0.05, 0.2 and 0.5% from weaning to 18 weeks of age, after which adenoma numbers were scored. Resveratrol at 0.05, 0.2 and 0.5% in the diet reduced adenoma number to 97 ± 31, 73 ± 10, and 70 ± 13 % of numbers in untreated controls, respectively; the decrease of adenoma number at the two higher doses compared to control was significant (p<0.05). DMU212 at the same doses reduced adenoma number to 85 ± 16, 76 ± 8 and 88 ± 22 % of control, respectively; here the decrease was significant only in the case of the 0.2 % dose (p<0.05). Expression of COX-2, which is thought to contribute to cancer progression and is a target of resveratrol, was measured by Western blotting in the human-derived colon cell lines HCEC and HCA-7. Resveratrol inhibited COX-2 expression in both cell lines at concentrations of 5μM and above, whilst DMU212 had a marginal effect, which was significant only at 50μM in HCEC cells. In order to compare the pharmacokinetic properties of these stilbenes, mice received them at 240 mg/kg via the intragastric route and drug concentrations were measured by HPLC in plasma and small intestinal and colonic mucosa. The ratios of area of plasma or target tissue concentration versus time curves of resveratrol over DMU 212 were 3.5, 0.1 and 0.15 for the plasma, small intestinal and colonic mucosa, respectively. The results suggest that whilst DMU212 is more available than resveratrol in the small intestine and colon, both agents seem to exert adenoma retarding activity in the ApcMin/+ mouse to a comparable extent.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]