Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice

Haidan M El-Shorbagy, Shaymaa M Eissa, Salwa Sabet, Akmal A El-GhorDepartment of Zoology, Faculty of Science, Cairo University, Giza, EgyptBackground: Several in vitro studies have revealed that zinc oxide nanoparticles (ZnO-NPs) were able to target cancerous cells selectively with minimal damage to...

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Autores principales:	El-Shorbagy HM, Eissa SM, Sabet S, El-Ghor AA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	ZnO-NPs antitumor ESC NAC oxidative stress and DNA damage Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/04e145fafa1f45bc96b72ce0419b00f6
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spelling	oai:doaj.org-article:04e145fafa1f45bc96b72ce0419b00f62021-12-02T04:44:56ZApoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice1178-2013https://doaj.org/article/04e145fafa1f45bc96b72ce0419b00f62019-05-01T00:00:00Zhttps://www.dovepress.com/apoptosis-and-oxidative-stress-as-relevant-mechanisms-of-antitumor-act-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Haidan M El-Shorbagy, Shaymaa M Eissa, Salwa Sabet, Akmal A El-GhorDepartment of Zoology, Faculty of Science, Cairo University, Giza, EgyptBackground: Several in vitro studies have revealed that zinc oxide nanoparticles (ZnO-NPs) were able to target cancerous cells selectively with minimal damage to healthy cells.Purpose: In the current study, we aimed to evaluate the antitumor activity of ZnO-NPs in Ehrlich solid carcinoma (ESC) bearing mice by measuring their effect on the expression levels of P53, Bax and Bcl2 genes as indicators of apoptotic induction in tumor tissues. Also, we assessed the potential ameliorative or potentiation effect of 100 mg/kg N-acetyl cysteine (NAC) in combination with ZnO-NPs.Materials and methods: ESC bearing mice were gavaged with three different doses of ZnO-NPs (50, 300 and 500 mg/kg body weight) alone or in combination with NAC for seven consecutive days. In addition to measuring the tumor size, pathological changes, zinc content, oxidative stress biomarkers and DNA damage in ESC, normal muscle, liver and kidney tissues were assessed.Results: Data revealed a significant reduction in tumor size with a significant increase in p53 and Bax and decrease in Bcl2 expression levels in the tissues of ZnO-NPs treated ESC bearing mice. Moreover, a significant elevation of MDA accompanied with a significant reduction of CAT and GST. Also, a marked increase in all comet assay parameters was detected in ZnO-NPs treated groups. On the other hand, the combined treatment with ZnO-NPs and NAC significantly reduced reactive oxygen species production and DNA damage in liver and kidney tissues in all ZnO-NPs treated groups.Conclusion: ZnO-NPs exhibited a promising anticancer efficacy in ESC, this could serve as a foundation for developing new cancer therapeutics. Meanwhile, the combined treatment with ZnO-NPs and NAC could act as a protective method for the healthy normal tissue against ZnO-NPs toxicity, without affecting its antitumor activity.Keywords: ZnO-NPs, antitumor, Ehrlich solid carcinoma, N-acetyl cysteine, oxidative stress, DNA damageEl-Shorbagy HMEissa SMSabet SEl-Ghor AADove Medical PressarticleZnO-NPsantitumorESCNACoxidative stress and DNA damageMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3911-3928 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	ZnO-NPs antitumor ESC NAC oxidative stress and DNA damage Medicine (General) R5-920
spellingShingle	ZnO-NPs antitumor ESC NAC oxidative stress and DNA damage Medicine (General) R5-920 El-Shorbagy HM Eissa SM Sabet S El-Ghor AA Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice
description	Haidan M El-Shorbagy, Shaymaa M Eissa, Salwa Sabet, Akmal A El-GhorDepartment of Zoology, Faculty of Science, Cairo University, Giza, EgyptBackground: Several in vitro studies have revealed that zinc oxide nanoparticles (ZnO-NPs) were able to target cancerous cells selectively with minimal damage to healthy cells.Purpose: In the current study, we aimed to evaluate the antitumor activity of ZnO-NPs in Ehrlich solid carcinoma (ESC) bearing mice by measuring their effect on the expression levels of P53, Bax and Bcl2 genes as indicators of apoptotic induction in tumor tissues. Also, we assessed the potential ameliorative or potentiation effect of 100 mg/kg N-acetyl cysteine (NAC) in combination with ZnO-NPs.Materials and methods: ESC bearing mice were gavaged with three different doses of ZnO-NPs (50, 300 and 500 mg/kg body weight) alone or in combination with NAC for seven consecutive days. In addition to measuring the tumor size, pathological changes, zinc content, oxidative stress biomarkers and DNA damage in ESC, normal muscle, liver and kidney tissues were assessed.Results: Data revealed a significant reduction in tumor size with a significant increase in p53 and Bax and decrease in Bcl2 expression levels in the tissues of ZnO-NPs treated ESC bearing mice. Moreover, a significant elevation of MDA accompanied with a significant reduction of CAT and GST. Also, a marked increase in all comet assay parameters was detected in ZnO-NPs treated groups. On the other hand, the combined treatment with ZnO-NPs and NAC significantly reduced reactive oxygen species production and DNA damage in liver and kidney tissues in all ZnO-NPs treated groups.Conclusion: ZnO-NPs exhibited a promising anticancer efficacy in ESC, this could serve as a foundation for developing new cancer therapeutics. Meanwhile, the combined treatment with ZnO-NPs and NAC could act as a protective method for the healthy normal tissue against ZnO-NPs toxicity, without affecting its antitumor activity.Keywords: ZnO-NPs, antitumor, Ehrlich solid carcinoma, N-acetyl cysteine, oxidative stress, DNA damage
format	article
author	El-Shorbagy HM Eissa SM Sabet S El-Ghor AA
author_facet	El-Shorbagy HM Eissa SM Sabet S El-Ghor AA
author_sort	El-Shorbagy HM
title	Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice
title_short	Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice
title_full	Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice
title_fullStr	Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice
title_full_unstemmed	Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice
title_sort	apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of zno-nps alone and in combination with n-acetyl cysteine in tumor-bearing mice
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/04e145fafa1f45bc96b72ce0419b00f6
work_keys_str_mv	AT elshorbagyhm apoptosisandoxidativestressasrelevantmechanismsofantitumoractivityandgenotoxicityofznonpsaloneandincombinationwithnacetylcysteineintumorbearingmice AT eissasm apoptosisandoxidativestressasrelevantmechanismsofantitumoractivityandgenotoxicityofznonpsaloneandincombinationwithnacetylcysteineintumorbearingmice AT sabets apoptosisandoxidativestressasrelevantmechanismsofantitumoractivityandgenotoxicityofznonpsaloneandincombinationwithnacetylcysteineintumorbearingmice AT elghoraa apoptosisandoxidativestressasrelevantmechanismsofantitumoractivityandgenotoxicityofznonpsaloneandincombinationwithnacetylcysteineintumorbearingmice
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Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice

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