Chemopreventive activity of crude hydroxsymatairesinol (HMR) extract in 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 inulin and HMR when compared with the inulin and inulin/rye bran fed mice (39.6+/-8.9 and 36.0+/-7.4, respectively). HMR resulted in normalization of beta-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-beta-catenin pathway. In the cytosolic fraction, beta-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, beta-catenin in the inulin (3.15+/-2.9 relative units) and inulin/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 beta-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).
Oikarinen
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SI
Department of Applied Chemistry and Microbiology (Nutrition), University of Helsinki, P.O. Box 27, FIN-00014, Helsinki, Finland.
Pajari
A
A
Mutanen
M
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D000236:Adenoma / Q000378:metabolism / Q000517:prevention & control; D011125:Adenomatous Polyposis Coli / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D007421:Intestine, Small / Q000473:pathology; D007444:Inulin / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental; D010936:Plant Extracts / Q000494:pharmacology; D012434:Secale; D015534:Trans-Activators; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D005663:Furans; D017705:Lignans; D010936:Plant Extracts; D015534:Trans-Activators; D051176:beta Catenin; D007444:Inulin