Whole blueberry powder modulates the growth and metastasis of MDA-MB-231 triple negative breast tumors in nude mice - PubMed (original) (raw)

Comparative Study

. 2011 Oct;141(10):1805-12.

doi: 10.3945/jn.111.140178. Epub 2011 Aug 31.

Affiliations

Comparative Study

Whole blueberry powder modulates the growth and metastasis of MDA-MB-231 triple negative breast tumors in nude mice

Lynn S Adams et al. J Nutr. 2011 Oct.

Abstract

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 5 and 10% BB-fed mice and cell death (Caspase 3) was greater in the 10% BB-fed mice compared to control mice (P ≤ 0.05). 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 IFNγ. To confirm effects on Wnt signaling, analysis of tumor tissues from 5% BB-fed mice revealed lower β-catenin expression and glycogen synthase kinase-3β phosphorylation with greater expression of the β-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.

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Conflict of interest statement

Author disclosures: L. S. Adams, N. Kanaya, S. Phung, Z. Liu, and S. Chen, no conflicts of interest.

Figures

FIGURE 1

FIGURE 1

MDA-MB-231 tumor volume (A), proliferation (B), and apoptosis (C) in female nude mice fed control, 5% BB powder, or 10% BB powder diet for 8 wk. Data are means ± SEM, n = 6. In A, labeled means at a time without a common letter differ, P ≤ 0.05. In B and C, asterisks indicate different from control: *P ≤ 0.05, **P ≤ 0.01. BB, blueberry.

FIGURE 2

FIGURE 2

β-Catenin (A), pGSK-3β (ΒB), and APC (C) expression in orthotopic MDA-MB-231 mammary tumors of female nude mice fed control or 5% BB diet for 7 wk. (A) Immunostaining staining intensity was graded as 1 (weak), 2 (moderate), or 3 (strong). (B,C) Three separate Western blots were quantified using Quantity One Software. Data are mean ± SEM, n = 15 (A) or 3 (means of triplicates) (B,C). Different from control, *P ≤ 0.05. APC, adenomatous polyposis coli; BB, blueberry; p-GSK, phospho-glycogen synthase kinase.

FIGURE 3

FIGURE 3

In situ tumor growth and metastasis monitored by Xenogen IVIS imaging at different time points after MDA-MB-231 tumor implantation in female nude mice fed control or 5% BB diet for 7 wk. (A) Orthotopic breast tumor growth from baseline to wk 5 postimplantation. (B) In situ and ex-vivo imaging of RLN and LLN lymph node metastasis at wk 5 postimplantation. (C) Frequency of metastasis and mean intensity of liver and LN metastases analyzed by contingency table. Intensity data are mean ± SEM for the number of mice with metastases. *Different from control, P ≤ 0.05. BB, blueberry; LLN, left lymph node; RLN, right lymph node.

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References

    1. Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology. 2008;52:108–18 - PubMed
    1. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44 - PubMed
    1. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23 - PMC - PubMed
    1. Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF, Macmillan D, Blamey RW, Ellis IO. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005;116:340–50 - PubMed
    1. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52 - PubMed

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