Histone deacetylase inhibitors stimulate the susceptibility of A549 cells to a plasma-activated medium treatment
Histone deacetylase inhibitors stimulate the susceptibility of A549 cells to a plasma-activated medium treatment
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DOI：
10.1016/j.abb.2016.07.019
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发表时间：
2016-09-15
影响因子：
3.9
通讯作者：
Hara, Hirokazu
中科院分区：
文献类型：
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作者：
Adachi, Tetsuo;Kano, Ayame;Hara, Hirokazu
近年来，非热大气压等离子体（NTAPP）放电在医学，特别是癌症治疗中的潜在应用数量有所增加。NTAPP已被证明不仅通过直接照射影响细胞，而且通过用预先制备的等离子体活化培养基（PAM）间接处理影响细胞。组蛋白去乙酰化酶（HDAC）抑制剂有可能提高抗癌药物和辐射的敏感性。本研究的目的是证明PAM和HDAC抑制剂联合应用对A549癌细胞存活的优势，并阐明潜在的机制。使用PAM和HDAC抑制剂（如阿司他汀A（TSA）和丙戊酸（VPA））的联合方案时，细胞核中DNA断裂的细胞死亡率高于单一PAM治疗，并伴有聚（ADP-核糖）聚合酶-1（PARP-1）的激活、ATP耗竭和细胞内钙水平升高。此外，Rad 51的表达，在同源重组途径中的DNA修复因子，显着抑制治疗与HDAC抑制剂。这些结果表明，HDAC抑制剂可以协同诱导癌细胞对PAM组分的敏感性。(C)2016 Elsevier Inc. All rights reserved.
The number of potential applications of non-thermal atmospheric pressure plasma (NTAPP) discharges in medicine, particularly in cancer therapy, has increased in recent years. NTAPP has been shown to affect cells not only by direct irradiation, but also by an indirect treatment with previously prepared plasma activated medium (PAM). Histone deacetylase (HDAC) inhibitors have the potential to enhance susceptibility to anticancer drugs and radiation. The aim of the present study was to demonstrate the advantage of the combined application of PAM and HDAC inhibitors on A549 cancer cell survival and elucidate the underlying mechanisms. Cell death with DNA breaks in the nucleus was greater using combined regimens of PAM and HDAC inhibitors such as trichostatin A (TSA) and valproic acid (VPA) than a single PAM treatment and was accompanied by the activation of poly (ADP-ribose) polymerase-1 (PARP-1), depletion of ATP, and elevations in intracellular calcium levels. Moreover, the expression of Rad 51, a DNA repair factor in homologous recombination pathways, was significantly suppressed by the treatment with HDAC inhibitors. These results demonstrate that HDAC inhibitors may synergistically induce the sensitivity of cancer cells to PAM components. (C) 2016 Elsevier Inc. All rights reserved.