Chemopreventive effects of North American cranberry (Vaccinium Macrocarpon) on colitis‐associated colon carcinogenesis in mice.

Abstract

North American cranberry (Vaccinium Macrocarpon), has been reported to have beneficial biological activities. In this study, we investigated the chemopreventive effects of North American cranberry on colitis‐associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)‐treated mice. It was observed that dietary administration of whole cranberry powder (WCP) significantly decreased colon tumor incidence, multiplicity, average tumor size and tumor burden. qRT‐PCR and ELISA results showed that both gene and protein expression levels of proinflammatory cytokines IL‐1, IL‐6 and TNF‐α were inhibited by WCP treatment. Immunoblotting results showed that administration of WCP resulted in profound effects on multiple proteins related with cell proliferation, inflammation and apoptosis. For example, WCP treatment significantly decreased the expression levels of COX‐2, PI3K/Akt, MMP‐2, MMP‐9, VEGF, EGFR, cyclin D, CDK4, Rb, and increased the levels of p53, p21, p27, cleaved caspase‐3 and cleaved PARP in colonic mucosa of AOM/DSS‐treated mice. Moreover, we found that treatment with WCP significantly enhanced the expression levels of phase II antioxidant enzymes, such as HO‐1 and NQO1 in colonic mucosa. Overall, our results demonstrated that dietary administration of WCP significantly inhibited colitis‐associated colon carcinogenesis in mice, providing a solid scientific basis for using North American cranberry as a chemopreventive agent for colon cancer in human.