Berries as chemopreventive dietary constituents--a mechanistic approach with the ApcMin/+ mouse.
Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We wanted to see if pure ellagic acid, natural ellagitannins and three wild berries have any effect on the adenoma formation in Apc- mutated Min/+ mice. Min/+ mice were fed high-fat AIN93-G diets containing 10% (w/w) freeze-dried bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), cloudberry (Rubus chamaemorus), cloudberry seeds or cloudberry pulp or pure ellagic acid at 1564 mg/kg for 10 weeks. beta-Catenin and cyclin D1 protein levels in the adenomas and in the normal-appearing mucosa were determined by Western blotting and immunohistochemistry. Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays. Three wild berries significantly reduced tumour number (15-30%, p < 0.05), and cloudberry and lingonberry also reduced tumour size by over 60% (p < 0.01). Cloudberry resulted in decreased levels of nuclear beta-catenin and cyclin D1 and lingonberry in the level of cyclin D1 in the large adenomas (p < 0.05). Affymetrix microarrays revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5f-nucleotidase and PGE2 receptor subtype EP4. Ellagic acid had no effect on the number or size of adenomas in the distal or total small intestine but it increased adenoma size in the duodenum when compared with the control diet (p < 0.05). Neither cloudberry seed nor pulp had any effect on the adenoma formation. Berries seem to have great potential as a source of chemopreventive components.
Mutanen
Marja
M
Department of Applied Chemistry and Microbiology (Nutrition), PO Box 66, 00014 University of Helsinki, Finland. marja.mutanen@helsinki.fi
Pajari
Anne-Maria
AM
Paivarinta
Essi
E
Misikangas
Marjo
M
Rajakangas
Johanna
J
Marttinen
Maija
M
Oikarinen
Seija
S
D000236:Adenoma / Q000235:genetics / Q000517:prevention & control*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004610:Ellagic Acid / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D017491:Genes, APC; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007414:Intestinal Neoplasms / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008817:Mice, Mutant Strains; D011897:Random Allocation; D051176:beta Catenin / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D047348:Hydrolyzable Tannins; D051176:beta Catenin; C013515:ellagitannin; D019938:Cyclin D1; D004610:Ellagic Acid