Oxidative Stress Induced by CuO Nanoparticles (CuO NPs) to Human Hepatocarcinoma (HepG2) Cells


The toxicity of CuO nanoparticles (CuO NPs) to human hepatocarcinoma (HepG2) cells was investigated in this study. CuO NPs (1 - 40 mg/L) had significant toxicity to HepG2 cells. The antioxidant N-acetyl-L-cysteine (NAC) significantly reduces the cytotoxicity induced by the CuO NPs, supporting the hypothesis that oxidative stress contributes to the cytotoxicity of CuO NPs. To further explore the oxidative mechanisms of cytotoxicity, we examined CuO NPs-induced production of reactive oxygen species (ROS) in HepG2 cells. CuO NPs generated intracellular ROS in HepG2 cells in a concentration-dependent manner.

Share and Cite:

Fu, X. (2015) Oxidative Stress Induced by CuO Nanoparticles (CuO NPs) to Human Hepatocarcinoma (HepG2) Cells. Journal of Cancer Therapy, 6, 889-895. doi: 10.4236/jct.2015.610097.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Serpone, N., Dondi, D. and Albini, A. (2007) Inorganic and Organic UV Filters: Their Role and Efficacy in Sunscreens and Suncare Products. Inorganica Chimica Acta, 360, 794-802.
[2] Dutta, A., Das, D., Grilli, M., Di, B.E., Traversa, E. and Chakravorty, D. (2003) Preparation of Solgel Nano-Composites Containing Copper Oxide and Their Gas Sensing Properties. Journal of Sol-Gel Science and Technology, 26, 1085-1089.
[3] Prinz, G.A. (1999) Magnetoelectronics. Science, 283, 330.
[4] Kobe, S., Drazic, G., McGuiness, P.J. and Strazisar, J. (2001) The Influence of the Magnetic Field on the Crystallisation Form of Calcium Carbonate and the Testing of a Magnetic Water-Treatment Device. Journal of Magnetism and Magnetic Materials, 236, 71-76.
[5] Jiang, L.C. and Zhang, W.D. (2010) A Highly Sensitive Nonenzymatic Glucose Sensor Based on CuO Nanoparticles-Modified Carbon Nanotube Electrode. Biosensors and Bioelectronics, 25, 1402-1407.
[6] Song, M.J., Hwang, S.W. and Whang, D. (2010) Non-Enzymatic Electrochemical CuO Nanoflowers Sensor for Hydrogen Peroxide Detection. Talanta, 80, 1648-1652.
[7] Xia, T., Kovochich, M., Liong, M., Madler, L., Gilbert, B., Shi, H., Yeh, J.I., Zink, J.I. and Nel, A.E. (2010) Comparison of the Mechanism of Toxicity of Zinc Oxide and Cerium Oxide Nanoparticles Based on Dissolution and Oxidative Stress Properties. ACS Nano, 2, 2121-2134.
[8] Maurer-Jones, M.A., Lin, Y. and Haynes, C.L. (2010) Functional Assessment of Metal Oxide Nanoparticle Toxicity in Immune Cells. ACS Nano, 4, 3363-3373.
[9] Wang, Z.Y., Li, N., Zhao, J., White, J.C., Qu, P. and Xing, B.S. (2012) CuO Nanoparticle Interaction with Human Epithelial Cells: Cellular Uptake, Location, Export, and Genotoxicity. Chemical Research in Toxicology, 25, 1512-1521.
[10] Fahmy, B. and Cormier, S.A. (2009) Copper Oxide Nanoparticles Induce Oxidative Stress and Cytotoxicity in Airway Epithelial Cells. Toxicol in Vitro, 23, 1365-1371.
[11] Ahamed, M., Siddiqui, M.A., Akhtar, M.J., Ahmad, I., Pant, A.B. and Alhadlaq, H.A. (2010) Genotoxic Potential of Copper Oxide Nanoparticles in Human Lung Epithelial Cells. Biochemical and Biophysical Research Communications, 396, 578-583.
[12] Sun, J., Wang, S.C., Zhao, D., Hun, F.H., Weng, L. and Liu, H. (2011) Cytotoxicity, Permeability, and Inflammation of Metal Oxide Nanoparticles in Human Cardiac Microvascular Endothelial Cells: Cytotoxicity, Permeability, and Inflammation of Metal Oxide Nanoparticles. Cell Biology and Toxicology, 27, 333-342.
[13] Xu, J., Li, Z., Xu, P., Xiao, L. and Yang, Z. (2012) Nanosized Copper Oxide Induces Apoptosis through Oxidative Stress in Podocytes. Archives of Toxicology, 87, 1067-1073.
[14] Perreault, F., Melegari, S.P., Costa, C.H., Rossetto, A.-F., Popovic, R. and Matias, W.G. (2012) Genotoxic Effects of Copper Oxide Nanoparticles in Neuro 2A Cell Cultures. Science of the Total Environment, 441, 117-124.
[15] Nishimori, H., Kondoh, M., Isoda, K., Tsunoda, S., Tsutsumi, Y. and Yagi, K. (2009) Silica Nanoparticles as Hepatotoxicants. European Journal of Pharmaceutics and Biopharmaceutics, 72, 496-501.
[16] Xie, G., Sun, J., Zhong, G., Shi, L. and Zhang, D. (2010) Biodistribution and Toxicity of Intravenously Administered Silica Nanoparticles in Mice. Archives of Toxicology, 84, 183-190.
[17] Wang, Y., Aker, W.G., Hwang, H.M., Yedjou, C.G., Yu, H. and Tchounwou, P.B. (2011) A Study of the Mechanism of in Vitro Cytotoxicity of Metal Oxide Nanoparticles Using Catfish Primary Hepatocytes and Human HepG2 Cells. Science of the Total Environment, 409, 4753-4762.
[18] Piret, J.P., Jacques, D., Audinot, J.N., Mejia, J., Boilan, E. and Noel, F. (2012) Copper (II) Oxide Nanoparticles Penetrate into HepG2 Cells, Exert Cytotoxicity via Oxidativestress and Induce Pro-Inflammatory Response. Nanoscale, 4, 7168-7184.
[19] Siddiqui, M.A., Alhadlaq, H.A., Ahmad, J., Al-Khedhairy, A.A., Musarrat, J. and Ahamed, M. (2013) Copper Oxide Nanoparticles Induced MitochondriaMediated Apoptosis in Human Hepatocarcinoma Cells. PLoS ONE, 8, e69534.
[20] Wang, Z.Y., Li, J., Zhao, J. and Xing, B.S. (2011) Toxicity and Internalization of CuO Nanoparticles to Prokaryotic Alga Microcystis Aeruginosa as Affected by Dissolved Organic Matter. Environmental Science & Technology, 45, 6032-6040.
[21] Gunawan, C., Teoh, W.Y., Marquis, C.P. and Amal, R. (2011) Cytotoxic Origin of Copper(II) Oxide Nanoparticles: Comparative Studies with Micron-Sized Particles, Leachate, and Metal Salts. ACS Nano, 5, 7214-7225.
[22] Zhao, J., Wang, Z.Y., Liu, X.Y., Xie, X.Y., Zhang, K. and Xing, B.S. (2011) Distribution of CuO Nanoparticles in Juvenile Carp (Cyprinus carpio) and Their Potential Toxicity. Journal of Hazardous Materials, 197, 304-310.
[23] Karlsson, H.L., Cronholm, P., Gustafsson, J. and Moller, L. (2008) Copper Oxide Nanoparticles Are Highly Toxic: A Comparison between Metal Oxide Nanoparticles and Carbon Nanotubes. Chemical Research in Toxicology, 21, 1726-1732.
[24] Siddiqui, M.A., Ahamed, M., Ahmad, J., Khan, M.A.M., Musarrat, J., Al-Khedhairy, A.A., et al. (2012) Nickel Oxide Nanoparticles Induce Cytotoxicity, Oxidative Stress and Apoptosis in Cultured Human Cells That Is Abrogated by the Dietary Antioxidant Curcumin. Food and Chemical Toxicology, 50, 641-647.
[25] Nel, A., Xia, T., Madler, L. and Li, N. (2006) Toxic Potential of Materials at the Nanolevel. Science, 311, 622-627.
[26] Asharani, P.V., Mun, G.K., Hande, M.P. and Valiyaveettil, S. (2009) Cytotoxicity and Genotoxicity of Silver Nanoparticles in Human Cells. ACS Nano, 3, 279-290.
[27] Ahamed, M., Akhtar, M.J., Raja, M., Ahmad, I., Siddiqui, M.K.J., AlSalhi, M.S., et al. (2011) Zinc Oxide Nanorod Induced Apoptosis via p53, bax/bcl-2 and Survivin Pathways in Human Lung Cancer Cells: Role of Oxidative Stress. Nanomedicine: Nanotechnology, Biology and Medicine, 7, 904-913.
[28] Trachootham, D., Alexandre, J. and Huang, P. (2009) Targeting Cancer Cells by ROS-Mediated Mechanisms: A Radical Therapeutic Approach? Nature Reviews Drug Discovery, 8, 579-591.
[29] Benz, C.C. and Yau, C. (2008) Ageing, Oxidative Stress and Cancer: Paradigms in Parallax. Nature Reviews Cancer, 8, 875-879.
[30] Jomova, K. and Valko, M. (2011) Advances in Metal-Induced Oxidative Stress and Human Disease. Toxicology, 283, 65-87.
[31] Boonstra, J. and Post, J.A. (2004) Molecular Events Associated with Reactive Oxygen Species and Cell Cycle Progression in Mammalian Cells. Gene, 337, 1-13.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.