Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells

Sunkui Ke,1 Tong Zhou,2 Peiyan Yang,3 Yange Wang,2 Peng Zhang,2 Keman Chen,2 Lei Ren,2 Shefang Ye2 1Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, 2Department of Biomaterials, College of Materials, Xiamen University, 3Department of Surgery, First Affiliated Hospital of Xia...

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Autores principales:	Ke S, Zhou T, Yang P, Wang Y, Zhang P, Chen K, Ren L, Ye S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	AuNPs TRAIL mitochondrial dynamics Drp1 Autophagy/mitophagy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cf98d2238e1d4be490e0f1d666b9cefc
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spelling	oai:doaj.org-article:cf98d2238e1d4be490e0f1d666b9cefc2021-12-02T04:21:03ZGold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells1178-2013https://doaj.org/article/cf98d2238e1d4be490e0f1d666b9cefc2017-03-01T00:00:00Zhttps://www.dovepress.com/gold-nanoparticles-enhance-trail-sensitivity-through-drp1-mediated-apo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sunkui Ke,1 Tong Zhou,2 Peiyan Yang,3 Yange Wang,2 Peng Zhang,2 Keman Chen,2 Lei Ren,2 Shefang Ye2 1Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, 2Department of Biomaterials, College of Materials, Xiamen University, 3Department of Surgery, First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of China Abstract: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agonistic receptors have been identified as highly promising antitumor agents preferentially eliminating cancer cells with minimal damage, the emergence of TRAIL resistance in most cancers may contribute to therapeutic failure. Thus, there is an urgent need for new approaches to overcome TRAIL resistance. Gold nanoparticles (AuNPs) are one of the most promising nanomaterials that show immense antitumor potential via targeting various cellular and molecular processes; however, the effects of AuNPs on TRAIL sensitivity in cancer cells remain unclear. In this study, we found that AuNPs combined with TRAIL exhibited a greater potency in promoting apoptosis in non-small-cell lung cancer (NSCLC) cells compared with TRAIL alone, suggesting that AuNPs sensitize cancer cells to TRAIL. Further experiments demonstrated that the combination of TRAIL and AuNPs was more effective in causing excessive mitochondrial fragmentation in cancer cells accompanied by a dramatic increase in mitochondrial recruitment of dynamin-related protein 1 (Drp1), mitochondrial dysfunctions, and enhancement of autophagy induction. Small interfering RNA (siRNA) silencing of Drp1 or inhibition of autophagy could effectively alleviate apoptosis in cells exposed to TRAIL combined with AuNPs. In vivo studies revealed that AuNPs augmented TRAIL sensitivity in tumor-bearing mice. Our data indicated that AuNPs potentiate apoptotic response to TRAIL in NSCLC cells through Drp1-dependent mitochondrial fission, and TRAIL combined with AuNPs can be a potential chemotherapeutic strategy for the treatment of NSCLC. Keywords: AuNPs, TRAIL, mitochondrial dynamics, Drp1, autophagy/mitophagyKe SZhou TYang PWang YZhang PChen KRen LYe SDove Medical PressarticleAuNPsTRAILmitochondrial dynamicsDrp1Autophagy/mitophagyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2531-2551 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	AuNPs TRAIL mitochondrial dynamics Drp1 Autophagy/mitophagy Medicine (General) R5-920
spellingShingle	AuNPs TRAIL mitochondrial dynamics Drp1 Autophagy/mitophagy Medicine (General) R5-920 Ke S Zhou T Yang P Wang Y Zhang P Chen K Ren L Ye S Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells
description	Sunkui Ke,1 Tong Zhou,2 Peiyan Yang,3 Yange Wang,2 Peng Zhang,2 Keman Chen,2 Lei Ren,2 Shefang Ye2 1Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, 2Department of Biomaterials, College of Materials, Xiamen University, 3Department of Surgery, First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of China Abstract: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agonistic receptors have been identified as highly promising antitumor agents preferentially eliminating cancer cells with minimal damage, the emergence of TRAIL resistance in most cancers may contribute to therapeutic failure. Thus, there is an urgent need for new approaches to overcome TRAIL resistance. Gold nanoparticles (AuNPs) are one of the most promising nanomaterials that show immense antitumor potential via targeting various cellular and molecular processes; however, the effects of AuNPs on TRAIL sensitivity in cancer cells remain unclear. In this study, we found that AuNPs combined with TRAIL exhibited a greater potency in promoting apoptosis in non-small-cell lung cancer (NSCLC) cells compared with TRAIL alone, suggesting that AuNPs sensitize cancer cells to TRAIL. Further experiments demonstrated that the combination of TRAIL and AuNPs was more effective in causing excessive mitochondrial fragmentation in cancer cells accompanied by a dramatic increase in mitochondrial recruitment of dynamin-related protein 1 (Drp1), mitochondrial dysfunctions, and enhancement of autophagy induction. Small interfering RNA (siRNA) silencing of Drp1 or inhibition of autophagy could effectively alleviate apoptosis in cells exposed to TRAIL combined with AuNPs. In vivo studies revealed that AuNPs augmented TRAIL sensitivity in tumor-bearing mice. Our data indicated that AuNPs potentiate apoptotic response to TRAIL in NSCLC cells through Drp1-dependent mitochondrial fission, and TRAIL combined with AuNPs can be a potential chemotherapeutic strategy for the treatment of NSCLC. Keywords: AuNPs, TRAIL, mitochondrial dynamics, Drp1, autophagy/mitophagy
format	article
author	Ke S Zhou T Yang P Wang Y Zhang P Chen K Ren L Ye S
author_facet	Ke S Zhou T Yang P Wang Y Zhang P Chen K Ren L Ye S
author_sort	Ke S
title	Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells
title_short	Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells
title_full	Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells
title_fullStr	Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells
title_full_unstemmed	Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells
title_sort	gold nanoparticles enhance trail sensitivity through drp1-mediated apoptotic and autophagic mitochondrial fission in nsclc cells
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/cf98d2238e1d4be490e0f1d666b9cefc
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_version_	1718401336167366656

Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells

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