Three Nordic berries inhibit intestinal tumorigenesis in multiple intestinal neoplasia/+ mice by modulating beta-catenin signaling in the tumor and transcription in the mucosa.
Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We studied the effects and molecular mechanisms of wild berries with different phenolic profiles on intestinal tumorigenesis in multiple intestinal neoplasia/+ mice. The mice were fed a high-fat AIN93-G diet (Con) or AIN93-G diets containing 10% (w:w) freeze-dried bilberry, lingonberry (LB), or cloudberry (CB) for 10 wk. All 3 berries significantly inhibited the formation of intestinal adenomas as indicated by a 15-30% reduction in tumor number (P < 0.05). CB and LB also reduced tumor burden by over 60% (P < 0.05). Compared to Con, CB and LB resulted in a larger (P < 0.05) proportion of small adenomas (43, 69, and 64%, respectively) and a smaller proportion of large adenomas (56, 29, and 33%, respectively). Beta-catenin and cyclin D1 in the small and large adenomas and in the normal-appearing mucosa were measured by Western blotting and immunohistochemistry. CB resulted in decreased levels of nuclear beta-catenin and cyclin D1 and LB in the level of cyclin D1 in the large adenomas (P < 0.05). Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays, which revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5'-nucleotidase, and prostaglandin E2 receptor subtype EP4. Our results indicate that berries are potentially a rich source of chemopreventive components.
Misikangas
Marjo
M
Department of Applied Chemistry and Microbiology (Nutrition), University of Helsinki, FIN-00014 Helsinki, Finland.
Pajari
Anne-Maria
AM
Päivärinta
Essi
E
Oikarinen
Seija I
SI
Rajakangas
Johanna
J
Marttinen
Maija
M
Tanayama
Heidi
H
Törrönen
Riitta
R
Mutanen
Marja
M
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D005638:Fruit / Q000737:chemistry*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008817:Mice, Mutant Strains; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D027824:Rosaceae / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic; D029796:Vaccinium / Q000737:chemistry*; D051176:beta Catenin / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D010936:Plant Extracts; D051176:beta Catenin; D019938:Cyclin D1