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Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

1
Department of Biology, University of Alabama at Birmingham, 1300 University Blvd, Birmingham, AL 35294, USA
2
School of Nursing, University of Alabama at Birmingham, 1701 University Blvd, Birmingham, AL 35294, USA
3
Comprehensive Cancer Center, University of Alabama at Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA
4
Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA
5
Nutrition Obesity Research Center, University of Alabama at Birmingham, 1675 University Blvd, Birmingham, AL 35294, USA
6
Comprehensive Diabetes Center, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(1), 23; https://doi.org/10.3390/cancers11010023
Received: 5 December 2018 / Revised: 18 December 2018 / Accepted: 18 December 2018 / Published: 27 December 2018
(This article belongs to the Special Issue Epigenetic Influence on Cancer Metastasis and/or Treatment Resistance)
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Abstract

Triple-negative breast cancer comprises approximately 15–20% of all breast cancers diagnosed and is nearly twice as common in black women than white women in the United States. We evaluated the effects of two epigenetic-modifying compounds on markers of growth potential in several triple-negative breast cancer cell lines. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor currently used in the treatment of cutaneous T cell lymphoma, was administered to triple-negative breast cancer cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. The compounds affected the expression of oncogenic miR-221/222 and tumor suppressors, p27 and PTEN, in addition to estrogen receptor alpha (ERα). E-cadherin expression was increased while N-cadherin was decreased, indicating a more epithelial phenotype. In addition, the activity of DNMTs was diminished with the treatments, and there was a significant enrichment of AcH3 within the promoter of p27 and PTEN, suggesting a role of epigenetic mechanisms for the aforementioned changes. These results translated to reduced migration of the triple-negative breast cancer cells with the treatments. Together, these findings support the role of SAHA and EGCG in limiting growth and proliferation of breast cancer cells. View Full-Text
Keywords: Mesenchymal-to-epithelial transition; breast cancer; DNMT inhibitors; HDAC inhibitors; phytochemicals; microRNA; cancer epigenetics Mesenchymal-to-epithelial transition; breast cancer; DNMT inhibitors; HDAC inhibitors; phytochemicals; microRNA; cancer epigenetics
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Lewis, K.A.; Jordan, H.R.; Tollefsbol, T.O. Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells. Cancers 2019, 11, 23.

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