Pro-Oxidant Therapeutic Activities of Cerium Oxide Nanoparticles in Colorectal Carcinoma Cells
Pro-Oxidant Therapeutic Activities of Cerium Oxide Nanoparticles in Colorectal Carcinoma Cells
复制标题
DOI：
10.1021/acsomega.9b04006
复制
发表时间：
2020-05-05
期刊：
影响因子：
4.1
通讯作者：
Roy, Somenath
中科院分区：
文献类型：
--
作者：
Datta, Aparna;Mishra, Snehasis;Roy, Somenath
鉴于癌细胞中活性氧（ROS）的基础水平较高，越来越多的学派认为促氧化剂是潜在的化疗药物。有趣的是，氧化铈（CeO 2）纳米粒子可以表现出抗氧化或促氧化活性作为不同的pH值的各种亚细胞定位的函数。在酸性pH环境中，例如，在癌细胞的细胞外环境中，CeO 2将起到促氧化剂的作用。基于这一概念，本研究旨在研究CeO 2在人大肠癌细胞系HCT 116中的促氧化活性。为了比较，我们还研究了二氧化铈纳米颗粒对人胚肾（HEK 293）细胞的影响。通过在培养基中用不同浓度（5-100 μ g/mL）的CeO 2纳米颗粒独立地处理癌细胞和正常细胞来评估癌细胞和正常细胞的剂量依赖性生存力。发现纳米氧化铈对HCT 116的半最大抑制浓度（IC 50）为50.48 μ g/mL，而对HEK 293细胞系的半最大抑制浓度（IC 50）为92.03 μ g/mL。为了了解CeO 2诱导细胞凋亡的复杂分子机制，进行了一系列实验。通过Annexin V-FITC染色、半胱天冬酶3/9分析、细胞色素c释放、细胞内ROS分析和使用流式细胞术的线粒体膜电位分析研究了纳米铈氧化物的凋亡诱导能力。实验数据表明，CeO 2处理通过增强ROS的产生导致DNA片段化，这最终通过p53依赖性线粒体信号通路导致细胞凋亡。
Given that basal levels of reactive oxygen species (ROS) are higher in cancer cells, there is a growing school of thought that endorses pro-oxidants as potential chemotherapeutic agents. Intriguingly, cerium oxide (CeO2) nanoparticles can manifest either anti- or pro-oxidant activity as a function of differential pH of various subcellular localizations. In an acidic pH environment, for example, in extracellular milieu of cancer cells, CeO2 would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO2 in human colorectal carcinoma cell line (HCT 116). For comparison, we have also studied the effect of ceria nanoparticles on human embryonic kidney (HEK 293) cells. Dose-dependent viability of cancerous as well as normal cells has been assessed by treating them independently with CeO2 nanoparticles of different concentrations (5-100 mu g/mL) in the culture media. The half maximal inhibitory concentration (IC50) of nanoceria for HCT 116 is found to be 50.48 mu g/mL while that for the HEK 293 cell line is 92.03 mu g/mL. To understand the intricate molecular mechanisms of CeO2-induced cellular apoptosis, a series of experiments have been conducted. The apoptosis-inducing ability of nanoceria has been investigated by Annexin V-FITC staining, caspase 3/9 analysis, cytochrome c release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO2 treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.