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.