Royston Kendra J, Udayakumar Neha, Lewis Kayla, Tollefsbol Trygve O
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.
Int J Mol Sci. 2017 May 19;18(5):1092. doi: 10.3390/ijms18051092.
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 and anti-apoptotic and found decreases in and increases in . 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.
癌症通常被归类为一种具有重要表观遗传成分的疾病，因此能够调节表观基因组的天然化合物成为了理想的研究对象。人类的饮食结构复杂，这表明需要阐明这些生物活性化合物之间的联合作用机制。来自印度冬樱的天然化合物 Withaferin A（WA）和来自十字花科蔬菜的萝卜硫素（SFN）具有多种抗癌作用，一些研究报告了它们调节表观遗传过程的能力。我们的研究首次调查了生理上可达到的低浓度 WA 和 SFN 对乳腺癌细胞增殖、组蛋白去乙酰化酶 1（HDAC1）和 DNA 甲基转移酶（DNMTs）的联合作用。在最佳浓度下，未观察到对对照细胞有不良影响。在 MCF-7 细胞中，联合处理对细胞活力有协同抑制作用，并且在 MDA-MB-231 和 MCF-7 细胞中，联合处理比单独使用任何一种化合物诱导的细胞凋亡更多。HDAC 的表达在多个水平上被下调。最后，我们确定了这些生物活性化合物对促凋亡和抗凋亡的联合作用，发现 减少而 增加。综上所述，我们的研究结果表明，低浓度的联合 WA 和 SFN 能够促进癌细胞死亡并调节人乳腺癌细胞中的关键表观遗传修饰因子。
