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

Royston, Kendra J.; Udayakumar, Neha; Lewis, Kayla; Tollefsbol, Trygve O.

doi:10.3390/ijms18051092

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

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Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA

Comprehensive Cancer Center, University of Alabama Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA

Comprehensive Center for Healthy Aging, University of Alabama Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA

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Nutrition Obesity Research Center, University of Alabama Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA

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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

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

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)

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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

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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. https://doi.org/10.3390/ijms18051092

AMA Style

Royston KJ, Udayakumar N, Lewis K, Tollefsbol TO. A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells. International Journal of Molecular Sciences. 2017; 18(5):1092. https://doi.org/10.3390/ijms18051092

Chicago/Turabian Style

Royston, Kendra J., Neha Udayakumar, Kayla Lewis, and Trygve O. Tollefsbol. 2017. "A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells" International Journal of Molecular Sciences 18, no. 5: 1092. https://doi.org/10.3390/ijms18051092

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

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