Skip to main content

Cerium Oxide Nanoparticles Induce Oxidative Stress and Genotoxicity in Human Skin Melanoma Cells

Cell Biochemistry and Biophysics volume 71, pages 1643–1651 (2015)Cite this article

Abstract

Extensive applications of cerium oxide (CeO2) nanoparticles require a better understanding of their possible effects on human health. However, data demonstrating the effect of CeO2 nanoparticles on the human skin melanoma cell remain scanty. In the current study, we determined the mechanism through which CeO2 nanoparticles (APS <25 nm) induce toxicity in human skin melanoma cells (A375). The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and neutral red uptake assays showed concentration and time-dependent cytotoxicity of CeO2 nanoparticles in A375 cells. CeO2 nanoparticles significantly induced the generation reactive oxygen species (ROS) and malondialdehyde, superoxide dismutase, and decreased glutathione levels in A375 cells. It was also observed that the CeO2 nanoparticles induced chromosomal condensation and caspase-3 activity. CeO2 nanoparticles exposed cells revealed the formation of DNA double-strand breakage as measured by percent tail DNA and olive tail moment through comet assay. The decline of cell viability, production of ROS, and DNA damage in A375 cells specifies that CeO2 nanoparticles have less capable to induce cyto and genotoxicity.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Riehemann, K., Schneider, S. W., Luger, T. A., Godin, B., Ferrari, M., & Fuchs, H. (2009). Nanomedicine-challenge and perspectives. Angewandte Chemie International Edition, 48, 872–897.

    Article  CAS  Google Scholar 

  2. Frohlich, E., & Roblegg, E. (2012). Models for oral uptake of nanoparticles in consumer products. Toxicology, 291, 10–17.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Eom, H. J., & Choi, J. (2009). Oxidative stress of CeO2 nanoparticles via p38-Nrf-2 signaling pathway in human bronchial epithelial cell, Beas-2B. Toxicology Letters, 187, 77–83.

    Article  CAS  PubMed  Google Scholar 

  4. Kim, I. S., Baek, M., & Choi, S. J. (2010). Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. Journal for Nanoscience and Nanotechnology, 10, 3453–3458.

    Article  CAS  Google Scholar 

  5. Singh, N., Manshian, B., Jenkins, G. J. S., Griffiths, S. M., Williams, P. M., Maffeis, T. G., et al. (2009). Nano Genotoxicology: The DNA damaging potential of engineered nanomaterials. Biomaterials, 30, 3891–3914.

    Article  CAS  PubMed  Google Scholar 

  6. Skocaj, M., Filipic, M., Petkovic, J., & Novak, S. (2011). Titanium dioxide in our everyday life; is it safe? Radiology and Oncology, 45, 227–247.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Li, Y.-F., & Chen, C. (2011). Fate and toxicity of metallic and metal-containing nanoparticles for biomedical applications. Small (Weinheim an der Bergstrasse, Germany), 7, 2965–2980.

    Article  CAS  Google Scholar 

  8. Wang, Y., Aker, W. G., Hwang, H. M., Yedjou, C. G., Yu, H., et al. (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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. van Maanen, J. M., Borm, P. J., Knaapen, A., van Herwijnen, M., Schilderman, P. A., Smith, K. R., et al. (1999). In vitro effects of coal fly ashes: Hydroxyl radical generation, iron release, and DNA damage and toxicity in rat lung epithelial cells. Inhalation Toxicology, 11, 1123–1141.

    Article  PubMed  Google Scholar 

  10. Borm, P. J., Schins, R. P., & Albrecht, C. (2004). Inhaled particles and lung cancer, part B: Paradigms and risk assessment. International Journal of Cancer, 110, 3–14.

    Article  CAS  Google Scholar 

  11. Alarifi, S., Ali, D., Alkahtani, S., Verma, A., Ahamed, M., Ahmed, M., et al. (2013). Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles. International Journal of Nanomedicine, 8, 983–993.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Ali, D., Verma, A., Mujtaba, F., Dwivedi, A., Hans, R. K., & Ray, R. S. (2011). UVB-induced apoptosis and DNA damaging potential of chrysene via reactive oxygen species in human keratinocytes. Toxicology Letters, 204, 199–207.

    Article  CAS  PubMed  Google Scholar 

  13. Suliman, A. Y., Ali, D., Alarifi, S., Harrath, A. H., Mansour, L., & Alwasel, S. H. (2013). Evaluation of cytotoxic, oxidative stress, proinflammatory and genotoxic effect of silver nanoparticles in human lung epithelial cells. Toxicology Environmental,. doi:10.1002/tox.21880.

    Google Scholar 

  14. Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248–254.

    Article  CAS  PubMed  Google Scholar 

  15. Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351–358.

    Article  CAS  PubMed  Google Scholar 

  16. Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82, 70–77.

    Article  CAS  PubMed  Google Scholar 

  17. Ali, D., Ray, R. S., & Hans, R. K. (2010). UVA-induced cyototoxicity and DNA damaging potential of Benz (e) acephenanthrylene in human skin cell line. Toxicology Letters, 199(2), 193–200.

    Article  CAS  PubMed  Google Scholar 

  18. Monteiro-Riviere, N. A., Inman, A. O., & Zhang, L. W. (2009). Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. Toxicology and Applied Pharmacology, 234(2), 222–235.

    Article  CAS  PubMed  Google Scholar 

  19. Horie, M., Nishio, K., Kato, H., Fujita, K., Endoh, S., Nakamura, A., et al. (2011). Cellular responses induced by cerium oxide nanoparticles: Induction of intracellular calcium level and oxidative stress on culture cells. Journal of Biochemistry, 150(4), 461–471.

    Article  CAS  PubMed  Google Scholar 

  20. Nel, A., Xia, T., Madler, L., & Li, N. (2006). Toxic potential of materials at the nano level. Science, 311, 622–627.

    Article  CAS  PubMed  Google Scholar 

  21. Xia, T., Kovochich, M., Brant, J., Hotze, M., Sempf, J., Oberley, T., et al. (2006). Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Letters, 6(8), 1794–1807.

    Article  CAS  PubMed  Google Scholar 

  22. Ott, M., Gogvadze, V., Orrenius, S., & Zhivotovsky, B. (2007). Mitochondria, oxidative stress and cell death. Apoptosis, 12, 913–922.

    Article  CAS  PubMed  Google Scholar 

  23. Rana, S. V. (2008). Metals and apoptosis: Recent developments. Journal of Trace Elements in Medicine and Biology, 22, 262–284.

    Article  CAS  PubMed  Google Scholar 

  24. Cheng, G., Guo, W., Han, L., Chen, E., Kong, L., Wang, L., et al. (2013). Cerium oxide nanoparticles induce cytotoxicity in human hepatoma SMMC-7721 cells via oxidative stress and the activation of MAPK signaling pathways. Toxicology in Vitro, 27(3), 1082–1088.

    Article  CAS  PubMed  Google Scholar 

  25. Kang, S. J., Kim, B. M., Lee, Y. J., & Chung, H. (2008). Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environmental and Molecular Mutagenesis, 49, 399–405.

    Article  CAS  PubMed  Google Scholar 

  26. Chen, M., & von Mikecz, A. (2005). Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Experimental Cell Research, 305(1), 51–62.

    Article  CAS  PubMed  Google Scholar 

  27. Collins, A. R. (2004). The comet assay for DNA damage and repair: Principles, applications and limitations. Molecular Biotechnology, 26(3), 249–261.

    Article  CAS  PubMed  Google Scholar 

  28. Martinez, G. R., Loureiro, A. P., Marques, S. A., Miyamoto, S., Yamaguchi, L. F., Onuki, J., et al. (2003). Oxidative and alkylating damage in DNA. Mutation Research, 544, 115–127.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the research Group Project No. RGP-VPP-180.

Conflict of interest

None.

Author information

Affiliations

  1. Department of Zoology, College of Science, King Saud University, BOX 2454, Riyadh, 11451, Saudi Arabia

    Daoud Ali, Saud Alarifi, Saad Alkahtani & Abdullah A. AlKahtane

  2. King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia

    Abdulaziz Almalik

Authors
  1. Daoud Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saud Alarifi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saad Alkahtani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdullah A. AlKahtane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdulaziz Almalik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daoud Ali.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ali, D., Alarifi, S., Alkahtani, S. et al. Cerium Oxide Nanoparticles Induce Oxidative Stress and Genotoxicity in Human Skin Melanoma Cells. Cell Biochem Biophys 71, 1643–1651 (2015). https://doi.org/10.1007/s12013-014-0386-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0386-6

Keywords

  • CeO2 nanoparticles
  • A375 cells
  • Oxidative stress
  • Apoptosis
  • DNA damage