HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells.
HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells.
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DOI：
10.17179/excli2016-186
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发表时间：
2016
期刊：
影响因子：
4.6
通讯作者：
Ekmekci A
中科院分区：
文献类型：
--
作者：
Yar Saglam AS;Yilmaz A;Onen HI;Alp E;Kayhan H;Ekmekci A
组蛋白脱乙酰酶 (HDAC) 通过改变组蛋白和非组蛋白的乙酰化状态，在染色质结构和基因表达的调节中发挥重要作用。 MS-275（entinostat，MS）是一种众所周知的基于苯甲酰胺的 HDACI，沙勒胺（SAL）是一种反向酰胺化合物 HDACI，对多种人类癌细胞具有抗增殖作用。在本研究中，我们旨在研究 HDACIs（MS 和 SAL）单独使用和/或与新型合成姜黄素类似物 EF24 (EF) 联合使用对人胰腺癌细胞系 (BxPC-3) 的影响。在体外，BxPC-3 细胞暴露于不同浓度的 MS、SAL（有或没有 EF），并测量它们对细胞活力、乙酰化组蛋白 H3 和 H4 水平、细胞毒性、裂解 caspase 3 水平以及细胞周期分布的影响。 EF、MS 和 SAL 处理后，BxPC-3 细胞的活力显着下降。 MS 和 SAL 处理以剂量依赖性方式增加组蛋白 H3 和 H4 的乙酰化。 MS和SAL单独使用或与EF联合使用均增加了G1期细胞的数量。此外，药物处理显着降低了G2/M期细胞的比例。 MS 治疗后，裂解的 Caspase 3 水平出现显着的剂量依赖性增加，但 SAL 治疗后则没有。我们的结果表明，HDAC 抑制剂（MS 和 SAL）与 EF 联合使用时，可以有效减少胰腺癌细胞 (BxPC-3) 的进展并将细胞周期停止在 G1 期。需要进一步的分子分析来了解胰腺癌细胞中 HDAC 抑制的基本分子后果。
Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells.