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Decrease of Reactive Oxygen Species-Related Biomarkers in the Tissue-Mimic 3D Spheroid Culture of Human Lung Cells Exposed to Zinc Oxide Nanoparticles
- Title
- Decrease of Reactive Oxygen Species-Related Biomarkers in the Tissue-Mimic 3D Spheroid Culture of Human Lung Cells Exposed to Zinc Oxide Nanoparticles
- Authors
- Kim, Eunjoo; Jeon, Won Bae; Kim, Soonhyun; Lee, Soo-Keun
- DGIST Authors
- Kim, Eunjoo; Jeon, Won Bae; Kim, Soonhyun; Lee, Soo-Keun
- Issue Date
- 2014-05
- Citation
- Journal of Nanoscience and Nanotechnology, 14(5), 3356-3365
- Type
- Article
- Article Type
- Article
- Keywords
- 3D Spheroid Culture; Amino Acids; Cell-to-Cell Signaling; Cell Culture; Cell Line, Tumor; Cell Proliferation; Cell Signaling; Cells; Collagen; Cytochrome C Oxidase; DNA Microarray; Elastin-Like Protein (ELP); Elastin-Like Proteins; Electron Transport Complex IV; Enzymology; Extracellular Matrices; Extracellular Matrix Proteins; Gene Expression; Gene Expression Profiles; Genetics; Human; Humans; Insulin-Like Growth Factor Binding Proteins; Lung Neoplasms; Lung Tumor; Messenger RNA; Metabolism; Metal Nanoparticle; Metal Nanoparticles; Microscopy, Electron, Scanning; Mitochondria; Mitochondrion; Morphology; Musculoskeletal System; Nanoparticle Toxicity; Nanoparticles; Nanotoxicity; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Oxygen; Pathology; Protein BCL 2; Proto-Oncogene Proteins C-BCL-2; Reactive Oxygen Metabolite; Reactive Oxygen Species (ROS); Respiratory System; RNA, Messenger; Scanning Electron Microscopy; Scleroprotein; Superoxide Dismutase; Three Dimensional; Tissue; Tumor Cell Line; Tumor Marker; Tumor Markers, Biological; Zinc Oxide; Zinc Oxide Nanoparticle; Zinc Oxide Nanoparticles
- ISSN
- 1533-4880
- Abstract
- Common 2-dimensional (2D) cell cultures do not adequately represent cell-cell and cell-matrix signaling and substantially different diffusion/transport pathways. To obtain tissue-mimic information on nanoparticle toxicity from in vitro cell tests, we used a 3-dimensional (3D) culture of human lung cells (A549) prepared with elastin-like peptides modified with an arginine-glycine-aspartate motif. The 3D cells showed different cellular phenotypes, gene expression profiles, and functionalities compared to the 2D cultured cells. In gene array analysis, 3D cells displayed the induced extracellular matrix (ECM)-related biological functions such as cell-to-cell signaling and interaction, cellular function and maintenance, connective tissue development and function, molecular transport, and tissue morphology. Additionally, the expression of ECM-related molecules, such as laminin, fibronectin, and insulin-like growth factor binding protein 3 (IGFBP3), was simultaneously induced at both mRNA and protein levels. When 0.08-50 μg/ml zinc oxide nanoparticles (ZnO-NPs) were administered to 2D and 3D cells, the cell proliferation was not significantly changed. The level of molecular markers for oxidative stress, such as superoxide dismutase (SOD), Bcl-2, ATP synthase, and Complex IV (cytochrome C oxidase), was significantly reduced in 2D culture when exposed to 10 μg/ml ZnO-NPs, but no significant decrease was detected in 3D culture when exposed to the same concentration of ZnO-NPs. In conclusion, the tissue-mimic phenotype and functionality of 3D cells could be achieved through the elevated expression of ECM components. The 3D cells were expected to help to better predict the nanotoxicity of ZnO-NPs at tissue-level by increased cell-cell and cell-ECM adhesion and signaling. The tissue-mimic morphology would also be useful to simulate the diffusion/transport of the nanoparticles in vitro. Copyright © 2014 American Scientific Publishers.
- URI
- http://hdl.handle.net/20.500.11750/5257
- DOI
- 10.1166/jnn.2014.8257
- Publisher
- American Scientific Publishers
- Related Researcher
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- Files:
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- Collection:
- Companion Diagnostics and Medical Technology Research Group1. Journal Articles
Smart Textile Convergence Research Group1. Journal Articles
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