Dietary supplementation with tart cherries for prevention of inflammation‐associated colorectal cancer in mice

Abstract

The cherry fruit is a nutrient‐dense food with comparatively low caloric content and significant amounts of key nutrients and bioactive food chemicals. Much of the health benefit of cherries is attributed to their high amounts of anthocyanins, which have anti‐oxidant and anti‐cancer properties that contribute to changes in cell signaling pathways involved in inflammation, carcinogenesis and angiogenesis. In this project, we aimed to determine whether dietary supplementation with tart cherries prevents colon tumor development in mice consuming a Western diet compared to a prudent diet. Previously, our research team developed the Total Western Diet (TWD) for mice to emulate typical U.S. nutrition with respect to macro‐ (sugars, fats, and protein) and micronutrient (vitamin and mineral) contents (Hintze, et al. 2012 J Ag Food Chem 60(27): 6736–6742). Incorporating the TWD in pre‐clinical studies allows for the analysis of the impact of dietary bioactives or functional foods on tumor development in a physiological environment that reflects nutritional patterns of the average American. We hypothesized that dietary supplementation with freeze‐dried whole tart cherries would suppress development of colon tumors in a model of inflammation‐associated colorectal cancer. A 2×2 factorial design was employed, whereby mice were fed either AIN93G (optimized for rodent health) or the TWD, each with and without Montmorency tart cherry powder added to the diet for a total anthocyanin content of 188 mg/kg diet. Mice were initiated with 10 mg/kg azoxymethane and provided 1% dextran sodium sulfate (DSS) in their drinking water for 4 weeks to promote colonic inflammation and tumorigenesis. Necropsy and tumor assessment were performed after 15 weeks of treatment. TWD consumption markedly enhanced colitis (40‐fold increase in disease activity) and tumor multiplicity (near 6‐fold increase) compared to consumption of the AIN93G diet. Supplementation with tart cherry powder caused a significant 40% reduction (P<0.05) in tumor incidence in mice fed AIN93G, whereas tart cherries had no effect on tumor incidence in mice fed TWD. However, tart cherry powder supplementation did not significantly affect tumor multiplicity or tumor size in mice fed either basal diet. Moreover, addition of the tart cherry supplement did not significantly affect colitis disease activity. These data contrast with a prior observation by our group that green tea supplementation was effective at reducing development of aberrant crypts, but only in mice fed TWD. Collectively, these observations point to important interactions between basal diets and dietary bioactive supplements and underscore the need for careful consideration of the role of basal diet in dietary chemoprevention studies in rodents.Support or Funding InformationSupport was provided by the Utah Agricultural Experiment Station (project UTA‐01178) and USDA NIFA Grant No. 2014‐67017‐21755 to A.B.