Iron stimulates plasma-activated medium-induced A549 cell injury.
Iron stimulates plasma-activated medium-induced A549 cell injury.
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DOI：
10.1038/srep20928
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发表时间：
2016-02-11
影响因子：
4.6
通讯作者：
Hara H
中科院分区：
文献类型：
--
作者：
Adachi T;Nonomura S;Horiba M;Hirayama T;Kamiya T;Nagasawa H;Hara H
常压低温等离子体适用于活细胞，已成为治疗癌症的一种新技术。最近研究表明，血浆不仅通过直接照射影响细胞，还通过预先制备的血浆激活介质(PAM)间接处理细胞。铁是一种不可缺少的元素，但也有潜在的毒性，因为它在过氧化氢(H_2O_2)存在的情况下通过芬顿反应产生羟基自由基(·OH)。本研究旨在探讨铁在PAM诱导A549腺癌细胞凋亡中的作用。在PAM处理的细胞中，我们检测到·OH的产生和细胞内亚铁离子的升高，发现它们被铁络合剂抑制。在亚铁离子中观察到的海拔可能是由于它们从细胞内的铁库铁蛋白中释放出来的。羟基自由基致DNA损伤后，多聚ADP-核糖聚合酶-1被激活，NAD+和ATP耗竭，细胞内钙离子升高。正常细胞如平滑肌细胞和角质形成细胞对PAM的敏感性低于A549细胞。这些结果表明，在存在铁离子的情况下，PAM中的H_2O_2和/或·OH干扰了癌细胞的线粒体-核网络。
Non-thermal atmospheric pressure plasma is applicable to living cells and has emerged as a novel technology for cancer therapy. Plasma has recently been shown to affect cells not only by direct irradiation, but also by indirect treatments with previously prepared plasma-activated medium (PAM). Iron is an indispensable element but is also potentially toxic because it generates the hydroxyl radical (•OH) in the presence of hydrogen peroxide (H2O2) via the Fenton reaction. The aim of the present study was to demonstrate the contribution of iron to PAM-induced A549 adenocarcinoma cell apoptosis. We detected the generation of •OH and elevation of intracellular ferrous ions in PAM-treated cells and found that they were inhibited by iron chelator. The elevations observed in ferrous ions may have been due to their release from the intracellular iron store, ferritin. Hydroxyl radical-induced DNA injury was followed by the activation of poly(ADP-ribose) polymerase-1, depletion of NAD+ and ATP, and elevations in intracellular Ca2+. The sensitivities of normal cells such as smooth muscle cells and keratinocytes to PAM were less than that of A549 cells. These results demonstrated that H2O2 in PAM and/or •OH generated in the presence of iron ions disturbed the mitochondrial-nuclear network in cancer cells.