Pomegranate juice and specific components inhibit cell and molecular processes critical for metastasis of breast cancer

Abstract

Breast cancer is the most common cancer and the second leading cause of cancer death and morbidity among women in the western world. Pomegranate juice (PJ) and three of its specific components have been shown to inhibit processes involved in prostate cancer metastasis. If this also proves to be true for breast cancer, these natural treatments will be promising agents against breast cancer that can serve as potentially effective and nontoxic alternatives or adjuncts to the use of conventional selective estrogen receptor modulators for breast cancer prevention and treatment. To test this possibility, we have used two breast cancer cell lines, MDA-MB-231 cells (ER) and MCF7 (ER+), and the non-neoplastic cell line MCF10A. We show that, in addition to inhibiting growth of the breast cancer cells, PJ or a combination of its components luteolin (L) + ellagic acid (E) + punicic acid (P) increase cancer cell adhesion and decrease cancer cell migration but do not affect normal cells. These treatments also inhibit chemotaxis of the cancer cells to SDF1α, a chemokine that attracts breast cancer cells to the bone. We hypothesized that PJ and L + E + P stimulate expression of genes that increase adhesion and inhibit genes that stimulate cell migration and inhibit chemotaxis to SDF1α. Using qPCR, we confirmed these proposed effects on gene expression and in addition we found that a gene important in epithelial-to-meshenchymal transitions is decreased. We also found that pro-inflammatory cytokines/chemokines are significantly reduced by these treatments, thereby having the potential to decrease inflammation and its impact on cancer progression. Discovery that PJ and L + E + P are inhibitory of metastatic processes in breast cancer cells in addition to prostate cancer cells indicate that they are potentially a very effective treatment to prevent cancer progression in general.

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Acknowledgments

We thank Dr. E. Turley for the HMMR expression vector and Dr. C. Glackin for the Twist vector. This study was funded by the Portuguese Foundation for Science and Technology.

Conflict of interest

None of the authors have conflict of interest related to this study.

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Correspondence to Manuela Martins-Green.

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Rocha, A., Wang, L., Penichet, M. et al. Pomegranate juice and specific components inhibit cell and molecular processes critical for metastasis of breast cancer. Breast Cancer Res Treat 136, 647–658 (2012). https://doi.org/10.1007/s10549-012-2264-5

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Keywords

  • Chemotaxis
  • Adhesion
  • Migration
  • Gene expression
  • Cytokines