Whole Blueberry Powder Modulates the Growth and Metastasis of MDA-MB-231 Triple Negative Breast Tumors in Nude Mice

Previous studies in our laboratory demonstrated that blueberry (BB) extract exhibited antitumor activity against MDA-MB-231 triple negative breast cancer (TNBC) cells and decreased metastatic potential in vitro. The current study tested 2 doses of whole BB powder, 5 and 10% (wt:wt) in the diet, against MDA-MB-231 tumor growth in female nude mice. In this study, tumor volume was 75% lower in mice fed the 5% BB diet and 60% lower in mice fed the 10% BB diet than in control mice (P <= 0.05). Tumor cell proliferation (Ki-67) was lower in the Sand 10% BB-fed mice and cell death (Caspase 3) was greater in the 10% BB-fed mice compared to control mice (P <= 0.051. Gene analysis of tumor tissues from the 5% BB-fed mice revealed significantly altered expression of genes important to inflammation, cancer, and metastasis, specifically, Wnt signaling, thrombospondin-2, IL-13, and IFN gamma. To confirm effects on Writ signaling, analysis of tumor tissues from 5% BB-fed mice revealed lower beta-catenin expression and glycogen synthase kinase-3 beta phosphorylation with greater expression of the beta-catenin inhibitory protein adenomatous polyposis coli compared to controls. A second study tested the ability of the 5% BB diet to inhibit MDA-MB-231-luc-D3H2LN metastasis in vivo. In this study, 5% BB-fed mice developed 70% fewer liver metastases (P= 0.04) and 25% fewer lymph node metastases (P=0.09) compared to control mice. This study demonstrates the oral antitumor and metastasis activity of whole BB powder against TNBC in mice. J. Nutr. 141: 1805-1812, 2011.