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
- PMID: 21880954
- PMCID: PMC3174855
- DOI: 10.3945/jn.111.140178
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.
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
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
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
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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