Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells.
Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells.
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DOI：
10.2147/ijn.s140071
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发表时间：
2017
影响因子：
8
通讯作者：
Gurunathan S
中科院分区：
文献类型：
--
作者：
Bai DP;Zhang XF;Zhang GL;Huang YF;Gurunathan S
氧化锌纳米粒子（ZnO NPs）经常用于油漆、表面涂层和化妆品等工业产品，最近，它们在生物和生物医学应用中得到了探索。因此，本研究旨在研究 ZnO NPs 对人卵巢癌细胞 (SKOV3) 细胞毒性、细胞凋亡和自噬的影响。采用多种分析技术对结晶尺寸为 20 nm 的 ZnO 纳米颗粒进行了表征，包括紫外-可见光谱、X 射线衍射、透射电子显微镜、傅里叶变换红外光谱和原子力显微镜。使用一系列细胞测定来检查细胞毒性、细胞凋亡和自噬。细胞暴露于 ZnO NP 会导致细胞活力呈剂量依赖性丧失，并且在 ZnO NP 处理的细胞中观察到典型的细胞凋亡特征，例如变圆和粘附丧失、活性氧生成增强以及线粒体膜电位丧失。此外，用ZnO NPs处理的细胞显示出显着的双链DNA断裂，这从大量表达γ-H2AX和Rad51的细胞中得到了证据。 ZnO NP 处理的细胞显示 p53 和 LC3 上调，表明 ZnO NP 能够上调细胞凋亡和自噬。最后，Western blot 分析显示 Bax、caspase-9、Rad51、γ-H2AX、p53 和 LC3 上调，Bcl-2 下调。研究结果表明，ZnO NPs 能够通过活性氧的产生和氧化应激，在人卵巢细胞中诱导显着的细胞毒性、细胞凋亡和自噬。因此，这项研究表明，ZnO NPs 是合适的、固有的抗癌剂，因为它具有多种有利的特征，包括有利的带隙、静电荷、表面化学和氧化还原循环级联的增强。
Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3). ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays. Exposure of cells to ZnO NPs resulted in a dose-dependent loss of cell viability, and the characteristic apoptotic features such as rounding and loss of adherence, enhanced reactive oxygen species generation, and loss of mitochondrial membrane potential were observed in the ZnO NP-treated cells. Furthermore, the cells treated with ZnO NPs showed significant double-strand DNA breaks, which are gained evidences from significant number of γ-H2AX and Rad51 expressed cells. ZnO NP-treated cells showed upregulation of p53 and LC3, indicating that ZnO NPs are able to upregulate apoptosis and autophagy. Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-H2AX, p53, and LC3 and downregulation of Bcl-2. The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades.