Chemopreventive activity of hydroksymatairesinol in adenomatous polyposis colimultiple intestinal neoplasia (Apc)Min mice

We studied the effects of a lignan, hydroxymatairesinol (HMR), and rye bran on intestinal tumor development in adenomatous polyposis colimultiple intestinal neoplasia (Apc)Min mice. HMR showed a strong chemopreventive effect in this animal model. The mean number of adenomas in the small intestine was significantly lower (26.6±11.0, P<0.05) in mice fed the TNS tumor promoter insulin and HMR when compared with the insulin and insulin/rye bran fed mice (39.6±8.9 and 36.0±7.4, respectively). HMR resulted in normalization of β-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-β-catenin pathway. In the cytosolic fraction, β-catenin level in adenoma tissue was significantly elevated (P=0.008–0.013) in all the diet groups as compared with that of the surrounding mucosa. In the nuclear fraction, β-catenin in the insulin (3.15±2.9 relative units) and insulin/rye (5.17±6.94 relative units) groups was also significantly higher (P=0.003–0.009) in the adenoma tissue when compared with the surrounding mucosa (0.5±0.5 and 0.35±0.39 relative units). However, HMR was able to restore nuclear β-catenin level of the adenoma tissue (0.41±0.25 relative units) to the level found in the surrounding mucosa (0.36±0.28 relative units).