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Breast Cancer Research and Treatment

, Volume 149, Issue 3, pp 655–668 | Cite as

Potentiation of growth inhibition and epigenetic modulation by combination of green tea polyphenol and 5-aza-2′-deoxycytidine in human breast cancer cells

  • Tulika Tyagi
  • Justin N. Treas
  • Prathap Kumar S. Mahalingaiah
  • Kamaleshwar P. Singh
Preclinical study

Abstract

Epigenetic therapy by DNA demethylating agent 5-aza-2′-deoxycytidine (5-aza 2′dC) is clinically effective in acute myeloid leukemia; however, it has shown limited results in treatment of breast cancer and has significant toxicity to normal cells. Green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) has anti-cancer and DNA demethylating properties with no significant toxicity toward normal cells. Therefore, the objective of this study was to evaluate the therapeutic efficacy of a combination of non-toxic, low dose of 5-aza 2′ dC with EGCG, on growth inhibition of breast cancer cells. Human breast cancer cell lines (MCF-7, MDA-MB 231) and non-tumorigenic MCF-10A breast epithelial cells were treated with either 5-aza 2′ dC, EGCG, or their combination for 7 days. Cell growth inhibition was determined by cell count, cell viability, cell cycle, and soft agar assay, whereas genes expression changes were determined by quantitative real-time PCR and/or Western blot analysis. Histone modifications and global DNA methylation changes were determined by Western blot and RAPD-PCR, respectively. The results revealed significantly greater inhibition of growth of breast cancer cells by co-treatment with 5-aza 2′ dC and EGCG compared to individual treatments, whereas it has no significant toxicity to MCF-10A cells. This was further confirmed by gene expression analysis. Changes in DNA methylation and histone modifications were also greater in cells with combination treatment. Findings of this study suggest that potentiation of growth inhibition of breast cancer cells by 5-aza 2′ dC and EGCG combination treatment, at least in part, is mediated by epigenetic mechanism.

Keywords

Breast cancer Epigenetic therapy EGCG 5-Aza-2′-deoxycytidine 

Notes

Conflict of interest

The authors hereby disclose that there are no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work, and therefore there is no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Tulika Tyagi
    • 1
  • Justin N. Treas
    • 1
  • Prathap Kumar S. Mahalingaiah
    • 1
  • Kamaleshwar P. Singh
    • 1
  1. 1.Department of Environmental Toxicology, The Institute of Environmental and Human Health (TIEHH)Texas Tech UniversityLubbockUSA

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