Cranberries contain various constituents relevant to human health. Our previous study demonstrated the chemopreventive effects of whole cranberry against colon cancer in mice. In order to determine the role of different cranberry secondary metabolites in inhibiting colon cancer, cranberry ethyl acetate extract (EAE) and polyphenol extract (PPE) were obtained. The free-radical scavenging activities and chemical composition of the cranberry extracts were determined. EAE consisted of triterpenes and sterols and a trace amount of proanthocyanidins. PPE mainly contained polyphenol with a trace amount of triterpenes. The chemopreventive effects of orally administered EAE and PPE on colitis-associated colon carcinogenesis were determined in mice. Dietary EAE and PPE significantly suppressed tumor metrics without noticeable adverse effects. Gene expression levels of key proinflammatory cytokines were also attenuated by EAE and PPE in the mouse colon. In conclusion, the novel cranberry extracts may offer an efficacious and safe means to prevent colonic tumorigenesis in humans.

Scope There are growing interests in using a whole‐food‐based approach to prevent chronic diseases due to potential synergistic interactions among different bioactive components within the whole foods. North American cranberry (Vaccinium macrocarpon), a polyphenol‐rich fruit, has been shown to exert multiple beneficial health effects. Methods and results For the first time, the protective effects of whole cranberry powder (WCP) are determined against colitis‐associated mouse colon tumorigenesis induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). The results show that dietary administration of WCP (1.5%, w/w in the diet) significantly suppresses colon tumorigenesis as indicated by the reduced tumor incidence, multiplicity, burden, and average tumor size in WCP‐fed mice compared to the positive control mice. Both gene and protein expression levels of pro‐inflammatory cytokines IL‐1β, IL‐6, and TNF‐α are markedly attenuated by WCP treatment in the colon of AOM/DSS‐treated mice. Moreover, WCP profoundly modulates multiple signaling pathways/proteins related to inflammation, cell proliferation, apoptosis, angiogenesis, and metastasis in the colon, which is closely associated with the inhibitory effects of WCP on colon tumorigenesis. Conclusion Overall, the results demonstrate chemopreventive effects of WCP on colon tumorigenesis in mice, providing a scientific basis for using the whole cranberry as a functional food to promote colon health in humans.

Several traditional and newer cultivars of cranberry from various growing regions in North America are excellent sources of PACs, particularly the Howes, Mullica Queen and Early Black cultivars. PAC content may play a role in keeping quality.

Objectives Colon cancer is the third most common cancer in the U.S., and inflammatory bowel disease (IBD) patients are at a greater risk of developing colon carcinoma. Cranberries (Vaccinium macrocarpon) are a commonly grown crop in North America which contain constituents relevant to human health, including flavonoids, phenolics and terpenoids. Recently, we have demonstrated the chemopreventive effects of whole cranberry fruits against colitis and colon cancer in murine models. However, the secondary metabolites in cranberry fruit could play different contributions against colon carcinogenesis. Thus, comparing nonpolar (ECE) and polar extracts (DPE) of cranberries to determine their efficacy on colon carcinogenesis is desired. Methods Selected polyphenols and other constituents were determined using established methods: quantitative 1H NMR methods by Bruker Assure-RMS for triterpenoids, HPLC-DAD for anthocyanins and flavonol glycosides and proanthocyanidins by DMAC assay. Over half of ECE was made up of triterpenes and sterols and trace amount of proanthocyanidins. Over 70% of DPE was polyphenol and trace amount of triterpenes. Higher free-radical scavenging activity was found in DPE than ECE. Results Next, we determined the chemopreventive effects of ECE and DPE extracts against colitis-associated colon cancer in azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated mice. It was observed that oral administration of ECE and DPE extracts at physiologically achievable doses significantly suppressed the development of colitis-associated colon cancer, evidenced by decreased tumor incidence, multiplicity and burden, compared to the control group, while minimum side-effect was observed. ECE treatment also reversed the shortening of colon caused by colitis. qRT-PCR results showed that gene expression levels of proinflammatory cytokines IL-1, IL-6 and TNF-α were significantly attenuated by ECE and DPE interventions, in comparison to the control group. Conclusions In conclusion, our findings demonstrate that the novel cranberry extracts may offer an efficacious, safe and inexpensive means to prevent colonic tumorigenesis in humans, particularly for individuals with chronic inflammation. Funding Sources USDA-NIFA, Leo and Anne Albert Charitable Trust, UMass Cranberry Health Research Center/UMass President's S&T Initiative, and NIH.

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