Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.
Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.
复制标题
DOI：
10.1016/j.yexcr.2018.04.015
复制
发表时间：
2018-07-01
影响因子：
3.7
通讯作者：
Tollefsbol TO
中科院分区：
文献类型：
--
作者：
Royston KJ;Paul B;Nozell S;Rajbhandari R;Tollefsbol TO
关于组合膳食化合物对参与乳腺癌预防的表观遗传机制的调节作用知之甚少。人类饮食由多种成分组成，需要阐明某些化合物如何相互作用。Withaferin A（WA）发现于印度冬樱桃中，被记录为DNA甲基转移酶（DNMT）抑制剂，萝卜硫素（SFN）是一种在十字花科蔬菜中发现的众所周知的组蛋白脱乙酰酶（HDAC）抑制剂，是两种表观遗传修饰化合物，最近才被联合研究。使用DNMT和HDAC抑制剂逆转乳腺癌中某些基因的恶性表达已显示出相当大的前景。以前，我们发现SFN + WA协同促进乳腺癌细胞死亡。在此，我们确定这些化合物抑制MDA-MB-231和MCF-7乳腺癌中从S期到G2期的细胞周期进展。此外，我们证明了这种独特的表观遗传修饰化合物的组合下调细胞周期蛋白D1和CDK 4和pRB的水平;相反，E2 F mRNA和肿瘤抑制因子p21的水平独立于p53而增加。我们发现这些事件与不受限制的组蛋白甲基化的增加相一致。我们提出SFN + WA诱导的乳腺癌细胞死亡部分归因于表观遗传修饰，表观遗传修饰导致负责调节癌细胞衰老的关键基因的调节表达。
Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyl transferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence.
登录
查看更多内容
影响因子：
8
作者：
Hui, L.;Zheng, Y.;Foster, D. A.
通讯作者：
Foster, D. A.
影响因子：
7
作者：
Hon, Gary C.;Hawkins, R. David;Ren, Bing
通讯作者：
Ren, Bing
联合生物活性植物体通过ERα表达的表观遗传重新激活ER阴性乳腺癌中的他莫昔芬治疗。
影响因子：
4.6
作者：
Li Y;Meeran SM;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
5.6
作者：
Royston KJ;Udayakumar N;Lewis K;Tollefsbol TO
通讯作者：
Tollefsbol TO
影响因子：
4
作者：
Alkhalaf, M;El-Mowafy, AM
通讯作者：
El-Mowafy, AM