Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells

Ding-Ping Bai,1,* Xi-Feng Zhang,2,* Guo-Liang Zhang,3,4 Yi-Fan Huang,1 Sangiliyandi Gurunathan5 1Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University, Fuzhou, China; 2College of Biological and Pharmaceutical Engineering, Wuha...

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Autores principales:	Bai D, Zhang X, Zhang G, Huang Y, Gurunathan S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Zinc oxide nanoparticles human ovarian cancer cells SKOV3 mitochondrial membrane potential apoptosis DNA fragmentation autophagy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f91ce7b9ba184e79aa685918cd83cf99
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spelling	oai:doaj.org-article:f91ce7b9ba184e79aa685918cd83cf992021-12-02T02:42:14ZZinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells1178-2013https://doaj.org/article/f91ce7b9ba184e79aa685918cd83cf992017-09-01T00:00:00Zhttps://www.dovepress.com/zinc-oxide-nanoparticles-induce-apoptosis-and-autophagy-in-human-ovari-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ding-Ping Bai,1,* Xi-Feng Zhang,2,* Guo-Liang Zhang,3,4 Yi-Fan Huang,1 Sangiliyandi Gurunathan5 1Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University, Fuzhou, China; 2College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China; 3Dong-E-E-Jiao Co., Ltd., Shandong, China; 4National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Shandong, China; 5Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, Republic of Korea *These authors contributed equally to this work Background: Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3). Methods: ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays. Results: Exposure of cells to ZnO NPs resulted in a dose-dependent loss of cell viability, and the characteristic apoptotic features such as rounding and loss of adherence, enhanced reactive oxygen species generation, and loss of mitochondrial membrane potential were observed in the ZnO NP-treated cells. Furthermore, the cells treated with ZnO NPs showed significant double-strand DNA breaks, which are gained evidences from significant number of γ-H2AX and Rad51 expressed cells. ZnO NP-treated cells showed upregulation of p53 and LC3, indicating that ZnO NPs are able to upregulate apoptosis and autophagy. Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-H2AX, p53, and LC3 and downregulation of Bcl-2. Conclusion: The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades. Keywords: zinc oxide nanoparticles, human ovarian cancer cells SKOV3, mitochondrial membrane potential, apoptosis, DNA fragmentation, autophagyBai DZhang XZhang GHuang YGurunathan SDove Medical PressarticleZinc oxide nanoparticleshuman ovarian cancer cells SKOV3mitochondrial membrane potentialapoptosisDNA fragmentationautophagyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6521-6535 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Zinc oxide nanoparticles human ovarian cancer cells SKOV3 mitochondrial membrane potential apoptosis DNA fragmentation autophagy Medicine (General) R5-920
spellingShingle	Zinc oxide nanoparticles human ovarian cancer cells SKOV3 mitochondrial membrane potential apoptosis DNA fragmentation autophagy Medicine (General) R5-920 Bai D Zhang X Zhang G Huang Y Gurunathan S Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
description	Ding-Ping Bai,1,* Xi-Feng Zhang,2,* Guo-Liang Zhang,3,4 Yi-Fan Huang,1 Sangiliyandi Gurunathan5 1Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University, Fuzhou, China; 2College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China; 3Dong-E-E-Jiao Co., Ltd., Shandong, China; 4National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Shandong, China; 5Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, Republic of Korea *These authors contributed equally to this work Background: Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3). Methods: ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays. Results: Exposure of cells to ZnO NPs resulted in a dose-dependent loss of cell viability, and the characteristic apoptotic features such as rounding and loss of adherence, enhanced reactive oxygen species generation, and loss of mitochondrial membrane potential were observed in the ZnO NP-treated cells. Furthermore, the cells treated with ZnO NPs showed significant double-strand DNA breaks, which are gained evidences from significant number of γ-H2AX and Rad51 expressed cells. ZnO NP-treated cells showed upregulation of p53 and LC3, indicating that ZnO NPs are able to upregulate apoptosis and autophagy. Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-H2AX, p53, and LC3 and downregulation of Bcl-2. Conclusion: The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades. Keywords: zinc oxide nanoparticles, human ovarian cancer cells SKOV3, mitochondrial membrane potential, apoptosis, DNA fragmentation, autophagy
format	article
author	Bai D Zhang X Zhang G Huang Y Gurunathan S
author_facet	Bai D Zhang X Zhang G Huang Y Gurunathan S
author_sort	Bai D
title	Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
title_short	Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
title_full	Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
title_fullStr	Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
title_full_unstemmed	Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
title_sort	zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/f91ce7b9ba184e79aa685918cd83cf99
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_version_	1718402260490256384

Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells

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