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Title: Dietary Intake of Pterostilbene, a Constituent of Blueberries, Inhibits the B-catenin/p65 Downstream Signaling Pathway and Colon Carcinogenesis in Rats

Author
item PAUL, SHIBY - Rutgers University
item DECASTRO, ANDREW - Rutgers University
item LEE, HONG JIN - Rutgers University
item SMOLAREK, AMANDA - Rutgers University
item SO, JAE YOUNG - Rutgers University
item SIMI, BARBARA - Rutgers University
item WANG, CHUNG XIOU - Rutgers University
item ZHOU, RENPING - Rutgers University
item Rimando, Agnes
item SUH, NANJOO - Rutgers University

Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/4/2010
Publication Date: 1/8/2010
Citation: Paul, S., Decastro, A., Lee, H., Smolarek, A.K., So, J., Simi, B., Wang, C., Zhou, R., Rimando, A.M., Suh, N. 2010. Dietary Intake of Pterostilbene, a Constituent of Blueberries, Inhibits the B-catenin/p65 Downstream Signaling Pathway and Colon Carcinogenesis in Rats. Carcinogenesis. 31(7):1272-1278.

Interpretive Summary: In our previous study, pterostilbene, a phenolic compound found in blueberries, grapes, as well as other plants was found to effectively reduce the incidence and multiplicity of lesions in the colon of rats injected with the carcinogen azoxymethane (AOM). Our present study was to identify the chemopreventive potential of pterostilbene with colonic tumor formation as an end point, and to evaluate the mechanistic action of pterostilbene during development of colon cancer. Rats were given two AOM injections subcutaneously when they were 7 and 8 weeks old, and continuously fed the control or 40 ppm pterostilbene diet for 45 weeks. Overall analyses indicated that pterostilbene reduced colon tumor multiplicity in epithelial tissue. Pterostilbene decreased mucosal levels of the pro-inflammatory proteins. Colon tumors from pterostilbene fed animals showed reduced expression of inflammatory markers. In human colonic adenocarcinoma cells (HT-29 cells), pterostilbene was also shown to reduce the levels of proteins associated with colon cancer. Data from cell and animals studies, which showed pterostilbene suppress colon tumorigenesis, cell proliferation, as well as key inflammatory markers suggest the potential use of pterostilbene for colon cancer prevention.

Technical Abstract: Stilbenes are phytochemicals present in grapes, berries, peanuts and red wine. A widely studied stilbene, resveratrol (trans-3,5,4’-trihydroxystilbene), has been shown to exert antioxidant, anti-inflammatory, chemopreventive, and anti-aging effects in a number of biological systems. We reported earlier that pterostilbene (trans-3,5-dimethoxy-4’-hydroxystilbene), a structurally related stilbene found in blueberries, was effective in reducing the incidence and multiplicity of aberrant crypt foci formation in the colon of rats injected with azoxymethane (AOM). Our present study was to identify the chemopreventive potential of pterostilbene with colonic tumor formation as an end point, and further to evaluate the mechanistic action of pterostilbene during colon carcinogenesis. F344 rats were given two AOM injections subcutaneously when they were 7 and 8 weeks old, and continuously fed the control or 40 ppm pterostilbene diet for 45 weeks. Overall analyses indicated that pterostilbene reduced colon tumor multiplicity of non-invasive adenocarcinomas, lowered proliferating cell nuclear antigen, and down-regulated the expression of ß-catenin and cyclin D1. Pterostilbene decreased mucosal levels of the pro-inflammatory cytokines, TNF-a, IL-1ß and IL-4. Colon tumors from pterostilbene fed animals showed reduced expression of inflammatory markers as well as nuclear staining for phospho-p65, a key molecule in the NF-kB pathway. In HT-29 cells, pterostilbene reduced the protein levels of ß-catenin, cyclin D1 and c-MYC, altered the cellular localization of ß-catenin, and inhibited the phosphorylation of p65. Our data with pterostilbene in suppressing colon tumorigenesis, cell proliferation as well as key inflammatory markers in vivo and in vitro suggest the potential use of pterostilbene for colon cancer prevention.