Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species

Mohd Javed Akhtar1,2, Maqusood Ahamed3, Sudhir Kumar1, MA Majeed Khan3, Javed Ahmad4, Salman A Alrokayan31Department of Zoology, University of Lucknow, Lucknow, India; 2Fibre Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India; 3King Abdullah Institute for Nanotechnolog...

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Autores principales:	Javed Akhtar M, Ahamed M, Kumar S, Khan MM, Ahmad J, Alrokayan SA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a2674bff1af44227af65d6e8f6a9c1af
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spelling	oai:doaj.org-article:a2674bff1af44227af65d6e8f6a9c1af2021-12-02T01:13:02ZZinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species1176-91141178-2013https://doaj.org/article/a2674bff1af44227af65d6e8f6a9c1af2012-02-01T00:00:00Zhttp://www.dovepress.com/zinc-oxide-nanoparticles-selectively-induce-apoptosis-in-human-cancer--a9303https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Mohd Javed Akhtar1,2, Maqusood Ahamed3, Sudhir Kumar1, MA Majeed Khan3, Javed Ahmad4, Salman A Alrokayan31Department of Zoology, University of Lucknow, Lucknow, India; 2Fibre Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India; 3King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia; 4Department of Zoology, College of Science, King Saud University, Riyadh, Saudi ArabiaBackground: Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear.Methods and results: We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells.Conclusion: Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.Keywords: ZnO nanoparticles, cancer therapy, p53, apoptosis, ROSJaved Akhtar MAhamed MKumar SKhan MMAhmad JAlrokayan SADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 845-857 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Javed Akhtar M Ahamed M Kumar S Khan MM Ahmad J Alrokayan SA Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
description	Mohd Javed Akhtar1,2, Maqusood Ahamed3, Sudhir Kumar1, MA Majeed Khan3, Javed Ahmad4, Salman A Alrokayan31Department of Zoology, University of Lucknow, Lucknow, India; 2Fibre Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India; 3King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia; 4Department of Zoology, College of Science, King Saud University, Riyadh, Saudi ArabiaBackground: Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear.Methods and results: We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells.Conclusion: Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.Keywords: ZnO nanoparticles, cancer therapy, p53, apoptosis, ROS
format	article
author	Javed Akhtar M Ahamed M Kumar S Khan MM Ahmad J Alrokayan SA
author_facet	Javed Akhtar M Ahamed M Kumar S Khan MM Ahmad J Alrokayan SA
author_sort	Javed Akhtar M
title	Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
title_short	Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
title_full	Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
title_fullStr	Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
title_full_unstemmed	Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
title_sort	zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/a2674bff1af44227af65d6e8f6a9c1af
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_version_	1718403217113481216

Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species

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