Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells

Tianke Zhang,1,2 E Du,1 Yan Liu,1 Jun Cheng,2 Zhihong Zhang,1 Yong Xu,1 Shiyong Qi,1 Yue Chen1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, People’s Republic of China; 2Department of Anorectal Surgery, Tianjin Unio...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhang T, Du E, Liu Y, Cheng J, Zhang Z, Xu Y, Qi S, Chen Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	zinc oxide nanoparticles epigenetics histone modification methylation ezh2 runx3 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/546df13ee2ad476ca7609349cc78ef73
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:546df13ee2ad476ca7609349cc78ef73
record_format	dspace
spelling	oai:doaj.org-article:546df13ee2ad476ca7609349cc78ef732021-12-02T11:48:53ZAnticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells1178-2013https://doaj.org/article/546df13ee2ad476ca7609349cc78ef732020-03-01T00:00:00Zhttps://www.dovepress.com/anticancer-effects-of-zinc-oxide-nanoparticles-through-altering-the-me-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tianke Zhang,1,2 E Du,1 Yan Liu,1 Jun Cheng,2 Zhihong Zhang,1 Yong Xu,1 Shiyong Qi,1 Yue Chen1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, People’s Republic of China; 2Department of Anorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, People’s Republic of ChinaCorrespondence: Yue Chen; Shiyong QiDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, No. 23, Pingjiang Road, Hexi District, Tianjin 300211 Tel +86-18630913339; +86-022-88329692Email chenyue831106@126.com; yongshiqi@126.comPurpose: Zinc oxide nanoparticles (nZnO) have been widely used in the medicine field. Numerous mechanistic studies for nZnO’s anticancer effects are merely performed under high concentration exposure. However, possible anticancer mechanisms of epigenetic dysregulation induced by low doses of nZnO are unclear.Methods: nZnO were characterized and bladder cancer T24 cells were treated with nZnO for 48 hrs at different exposure concentrations. Cell cycle, apoptosis, cell migration and invasion were determined. We performed qRT-PCR, Western blot and chromatin immunoprecipitation to detect the mRNA and protein levels of signaling pathway cascades for histone modification.Results: In this study, we investigated the potential anticancer effects and mechanisms of nZnO on histone modifications in bladder cancer T24 cells upon low-dose exposure. Our findings showed that low concentrations of nZnO resulted in cell cycle arrest at S phase, facilitated cellular late apoptosis, repressed cell invasion and migration after 48 hrs exposure. These anticancer effects could be attributed to increased RUNX3 levels resulting from reduced H3K27me3 occupancy on the RUNX3 promoter, as well as decreased contents of histone methyltransferase EZH2 and the trimethylation of histone H3K27. Our findings reveal that nZnO are able to enter into the cytoplasm and nucleus of T24 cells. Additionally, both particles and ions from nZnO may jointly contribute to the alteration of histone methylation. Moreover, sublethal nZnO-conducted anticancer effects and epigenetic mechanisms were not associated with oxidative stress or DNA damage.Conclusion: We reveal a novel epigenetic mechanism for anticancer effects of nZnO in bladder cancer cells under low-dose exposure. This study will provide experimental basis for the toxicology and cancer therapy of nanomaterials.Keywords: zinc oxide nanoparticles, epigenetics, histone modification, methylation, EZH2, RUNX3Zhang TDu ELiu YCheng JZhang ZXu YQi SChen YDove Medical Pressarticlezinc oxide nanoparticlesepigeneticshistone modificationmethylationezh2runx3Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1457-1468 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	zinc oxide nanoparticles epigenetics histone modification methylation ezh2 runx3 Medicine (General) R5-920
spellingShingle	zinc oxide nanoparticles epigenetics histone modification methylation ezh2 runx3 Medicine (General) R5-920 Zhang T Du E Liu Y Cheng J Zhang Z Xu Y Qi S Chen Y Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells
description	Tianke Zhang,1,2 E Du,1 Yan Liu,1 Jun Cheng,2 Zhihong Zhang,1 Yong Xu,1 Shiyong Qi,1 Yue Chen1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, People’s Republic of China; 2Department of Anorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, People’s Republic of ChinaCorrespondence: Yue Chen; Shiyong QiDepartment of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, No. 23, Pingjiang Road, Hexi District, Tianjin 300211 Tel +86-18630913339; +86-022-88329692Email chenyue831106@126.com; yongshiqi@126.comPurpose: Zinc oxide nanoparticles (nZnO) have been widely used in the medicine field. Numerous mechanistic studies for nZnO’s anticancer effects are merely performed under high concentration exposure. However, possible anticancer mechanisms of epigenetic dysregulation induced by low doses of nZnO are unclear.Methods: nZnO were characterized and bladder cancer T24 cells were treated with nZnO for 48 hrs at different exposure concentrations. Cell cycle, apoptosis, cell migration and invasion were determined. We performed qRT-PCR, Western blot and chromatin immunoprecipitation to detect the mRNA and protein levels of signaling pathway cascades for histone modification.Results: In this study, we investigated the potential anticancer effects and mechanisms of nZnO on histone modifications in bladder cancer T24 cells upon low-dose exposure. Our findings showed that low concentrations of nZnO resulted in cell cycle arrest at S phase, facilitated cellular late apoptosis, repressed cell invasion and migration after 48 hrs exposure. These anticancer effects could be attributed to increased RUNX3 levels resulting from reduced H3K27me3 occupancy on the RUNX3 promoter, as well as decreased contents of histone methyltransferase EZH2 and the trimethylation of histone H3K27. Our findings reveal that nZnO are able to enter into the cytoplasm and nucleus of T24 cells. Additionally, both particles and ions from nZnO may jointly contribute to the alteration of histone methylation. Moreover, sublethal nZnO-conducted anticancer effects and epigenetic mechanisms were not associated with oxidative stress or DNA damage.Conclusion: We reveal a novel epigenetic mechanism for anticancer effects of nZnO in bladder cancer cells under low-dose exposure. This study will provide experimental basis for the toxicology and cancer therapy of nanomaterials.Keywords: zinc oxide nanoparticles, epigenetics, histone modification, methylation, EZH2, RUNX3
format	article
author	Zhang T Du E Liu Y Cheng J Zhang Z Xu Y Qi S Chen Y
author_facet	Zhang T Du E Liu Y Cheng J Zhang Z Xu Y Qi S Chen Y
author_sort	Zhang T
title	Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells
title_short	Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells
title_full	Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells
title_fullStr	Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells
title_full_unstemmed	Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells
title_sort	anticancer effects of zinc oxide nanoparticles through altering the methylation status of histone on bladder cancer cells
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/546df13ee2ad476ca7609349cc78ef73
work_keys_str_mv	AT zhangt anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT due anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT liuy anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT chengj anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT zhangz anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT xuy anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT qis anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells AT cheny anticancereffectsofzincoxidenanoparticlesthroughalteringthemethylationstatusofhistoneonbladdercancercells
_version_	1718395225925222400

Anticancer Effects of Zinc Oxide Nanoparticles Through Altering the Methylation Status of Histone on Bladder Cancer Cells

Ejemplares similares