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Berries as chemopreventive dietary constituents--a mechanistic approach with the ApcMin/+ mouse
Marja Mutanen1, Anne-Maria Pajari, Essi Paivarinta
1Department of Applied Chemistry and Microbiology (Nutrition), PO Box 66, 00014 University of Helsinki, Finland. marja.mutanen@helsinki.fi
Abstract:
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.
Insights
Wild berries significantly reduced adenoma formation in mice, with cloudberry and lingonberry showing notable reductions in tumor number and size. These berries may offer potential chemopreventive benefits against colon cancer.
Area of Science:
- Nutritional Science
- Cancer Research
- Pharmacology
Background:
- Berries possess compounds with proposed anticarcinogenic properties.
- Adenoma formation in Apc-mutated Min/+ mice serves as a model for studying colorectal cancer.
- Understanding berry's impact on tumor development is crucial for chemoprevention strategies.
Purpose of the Study:
- To investigate the effects of pure ellagic acid, ellagitannins, and three wild berries on adenoma formation in Min/+ mice.
- To analyze the impact of these compounds on beta-catenin and cyclin D1 protein levels.
- To explore early gene expression changes related to colon carcinogenesis.
Main Methods:
- Min/+ mice were fed diets containing bilberry, lingonberry, cloudberry, or ellagic acid for 10 weeks.
- Western blotting and immunohistochemistry were used to assess protein levels in adenomas and mucosa.
- Affymetrix microarrays analyzed gene expression changes in normal-appearing mucosa.
Main Results:
- Three wild berries significantly reduced tumor number (15-30%) and size (cloudberry and lingonberry >60%).
- Cloudberry and lingonberry decreased nuclear beta-catenin and cyclin D1 levels in adenomas.
- Gene expression analysis revealed altered pathways in colon carcinogenesis, including decreased expression of adenosine deaminase, ecto-5f-nucleotidase, and the PGE2 receptor EP4.
Conclusions:
- Wild berries, particularly cloudberry and lingonberry, demonstrate significant potential as sources of chemopreventive agents against adenoma formation.
- Ellagic acid did not show protective effects and even increased duodenal adenoma size.
- Berries contain bioactive compounds that modulate key pathways involved in colon cancer development.
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