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Int. J. Mol. Sci. 2017, 18(5), 1092; doi:10.3390/ijms18051092

A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells

1
Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA
2
Comprehensive Cancer Center, University of Alabama Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA
3
Comprehensive Center for Healthy Aging, University of Alabama Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA
4
Nutrition Obesity Research Center, University of Alabama Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA
5
Comprehensive Diabetes Center, University of Alabama Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Nicoletta Sacchi
Received: 15 April 2017 / Revised: 15 May 2017 / Accepted: 17 May 2017 / Published: 19 May 2017
(This article belongs to the Special Issue Cancer Epigenetics)
View Full-Text   |   Download PDF [3640 KB, uploaded 19 May 2017]   |  

Abstract

With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells. View Full-Text
Keywords: sulforaphane; withaferin; breast cancer; histone deacetylase1 (HDAC1); DNA methyltransferases (DNMTs); chemoprevention; epigenetics sulforaphane; withaferin; breast cancer; histone deacetylase1 (HDAC1); DNA methyltransferases (DNMTs); chemoprevention; epigenetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Royston, K.J.; Udayakumar, N.; Lewis, K.; Tollefsbol, T.O. A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells. Int. J. Mol. Sci. 2017, 18, 1092.

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