Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells.
Transcriptomics-Based Characterization of the Toxicity of ZnO Nanoparticles Against Chronic Myeloid Leukemia Cells.
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DOI：
10.2147/ijn.s261636
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发表时间：
2020
影响因子：
8
通讯作者：
Pepper C
中科院分区：
文献类型：
--
作者：
Alsagaby SA;Vijayakumar R;Premanathan M;Mickymaray S;Alturaiki W;Al-Baradie RS;AlGhamdi S;Aziz MA;Alhumaydhi FA;Alzahrani FA;Alwashmi AS;Al Abdulmonem W;Alharbi NK;Pepper C
纳米氧化锌作为一种潜在的抗癌药物，近年来引起了人们的关注。据我们所知，纳米氧化锌对人慢性粒细胞白血病细胞株(K562细胞)的毒性尚未用转录组学方法进行研究。本研究旨在评价纳米氧化锌诱导人慢性粒细胞白血病细胞(K562细胞)凋亡的能力，并探讨其可能的作用机制。采用细胞活力测定和流式细胞术，结合Annexin V-FITC和碘化丙啶，研究了纳米氧化锌对K562细胞和正常外周血单核细胞的毒性作用。接下来，我们利用基于DNA微阵列的转录组学方法研究了纳米氧化锌对K562细胞转录组的影响。氧化锌纳米颗粒对白血病细胞(p≤0.005)具有选择性毒性(主要是通过凋亡)并改变其转录组，在K562细胞中发现了4 2 9个折叠改变(Fc)≥4和p≤0.008校正p≤0.0 5的差异表达基因(DEG)。这些过表达的基因与“对锌的反应”、“对有毒物质的反应”和“对生长的负调控”有关(校正p≤0.05)。相反，被抑制的基因正向调控“细胞增殖”、“细胞迁移”、“细胞黏附”、“通过JAK-STAT的受体信号通路”和“磷脂酰肌醇3-激酶信号通路”(校正p≤0.05)。P≥0.0 5和校正p≤0.1使Fc降至1.5，表明≤纳米粒过表达抗氧化防御系统，促使K562细胞发生线粒体依赖性的凋亡，并靶向NF-κB途径。综上所述，我们的发现支持了早期报道的氧化锌纳米颗粒的抗癌活性，并揭示了氧化锌纳米颗粒诱导K562细胞凋亡的可能分子机制。
Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach. The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action. We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells. ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥4 and p≤0.008 with corrected p≤0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in “response to zinc”, “response to toxic substance” and “negative regulation of growth” (corrected p≤0.05). In contrast, the repressed genes positively regulated “cell proliferation”, “cell migration”, “cell adhesion”, “receptor signaling pathway via JAK-STAT” and “phosphatidylinositol 3-kinase signaling” (corrected p≤0.05). Lowering the FC to ≥1.5 with p≤0.05 and corrected p≤0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway. Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells.