Dietary intake of pterostilbene, a constituent of blueberries, inhibits the beta-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats
Paul S, DeCastro AJ, Lee HJ, Smolarek AK, So JY, Simi B, Wang CX, Zhou R, Rimando AM, Suh N
Carcinogenesis · 104 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- U.S. Department of Agriculture
- University or hospital
- Rutgers, The State University of New Jersey
- Government
- National Institute of Environmental Health Sciences
- Government
- NIEHS NIH HHS
- Grants
- National Institute of Environmental Health Sciences (P-30 ES-005022)
Based on 4 listed funder(s).
Publication
- Published
- 2010-01-08 · Carcinogenesis · vol. 31 · issue 7 · pp. 1272–1278
- Publisher
- Oxford University Press
- Cited
- 128 citations · more than 95% of similar papers · 4.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 56 works
- Access
- Open access (repository copy)
- Research areas
- Sirtuins and Resveratrol in Medicine · Cancer-related molecular mechanisms research · RNA modifications and cancer
- Keywords
- Pterostilbene, Azoxymethane, Carcinogenesis, Proinflammatory cytokine, Resveratrol, Cyclin D1, Cancer research, Aberrant crypt foci, Tumor necrosis factor alpha, Chemistry, Apoptosis, Cell cycle, Biology, Internal medicine, Biochemistry, Inflammation, Endocrinology, Immunology, Colorectal cancer, Medicine, Cancer
- MeSH
- ht29 cells, animals, rats, inbred f344, humans, rats, colonic neoplasms, azoxymethane, stilbenes, cyclin d1, proto-oncogene proteins c-myc, proliferating cell nuclear antigen, cytokines, signal transduction, phosphorylation, male, beta catenin, cyclooxygenase 2, transcription factor rela, nitric oxide synthase type ii
10 authors
From US
- Sattwikesh PaulRutgers, The State University of New Jersey; Environmental and Occupational Health Sciences Institute
- Andrew DeCastroRutgers, The State University of New Jersey
- H. J. LeeRutgers, The State University of New Jersey
- Amanda K. SmolarekRutgers, The State University of New Jersey
- Jae Young SoRutgers, The State University of New Jersey
- Barbara SimiRutgers, The State University of New Jersey
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 antiaging 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 p.p.m. pterostilbene diet for 45 weeks. Overall analyses indicated that pterostilbene reduced colon tumor multiplicity of non-invasive adenocarcinomas, lowered proliferating cell nuclear antigen and downregulated the expression of beta-catenin and cyclin D1. Pterostilbene decreased mucosal levels of the proinflammatory cytokines, tumor necrosis factor-alpha, interleukin (IL)-1beta 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 nuclear factor-kappaB pathway. In HT-29 cells, pterostilbene reduced the protein levels of beta-catenin, cyclin D1 and c-MYC, altered the cellular localization of beta-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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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