Combinatorial Epigenetic Mechanisms and Efficacy of Early Breast Cancer Inhibition by Nutritive Botanicals

Abstract

Aim: Aberrant epigenetic events are important contributors to the pathogenesis of different types of cancers and dietary botanicals with epigenetic properties can influence early cancer development leading to cancer prevention effects. We sought to investigate potential combinatorial effects of bioactive dietary components including green tea polyphenols (GTPs) and broccoli sprouts (BSp) on neutralizing epigenetic aberrations during breast tumorigenesis. Materials & methods: The combinatorial effects were evaluated in a breast cancer transformation cellular system and breast cancer mouse xenografts. Results & conclusion: Combined treatment with epigallocatechin-3-gallate in GTPs and sulforaphane in BSp resulted in a synergistic inhibition of breast cancer cellular growth. Further studies revealed this combination led to genome-wide epigenetic alterations. Combinatorial diets significantly inhibited tumor growth in breast cancer mouse xenografts. Collectively, these studies indicate that combined GTPs and BSp are highly effective in inhibiting early breast cancer development by, at least in part, regulating epigenetic mechanisms.

Keywords::

• breast tumorigenesis
• broccoli sprouts
• EGCG
• epigenetic
• green tea polyphenols
• sulforaphane

Author contributions

Y Li designed and conducted the experiments and drafted the manuscript. P Buckhaults assisted with some experiments and genome-wide DNA methylation analysis. XQ Cui assisted with genome-wide DNA methylation analysis. TO Tollefsbol conceived the study, contributed to the design of the experiments and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by grants from the National Cancer Institute (R01 CA178441; R03 CA176766) and the American Institute for Cancer Research (316184). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the National Cancer Institute (R01 CA178441; R03 CA176766) and the American Institute for Cancer Research (316184). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.