Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players

Sangiliyandi Gurunathan, Min-Hee Kang, Muniyandi Jeyaraj, Jin-Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaCorrespondence: Sangiliyandi Gurunathan; Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 0502...

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Autores principales:	Gurunathan S, Kang MH, Jeyaraj M, Kim JH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	exosome platinum nanoparticle cytotoxicity oxidative stress acetylcholinesterase activity neutral sphingomyelinase activity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/033dfeb6ca854516966c1a66026f40c6
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spelling	oai:doaj.org-article:033dfeb6ca854516966c1a66026f40c62021-12-02T16:01:13ZPlatinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players1178-2013https://doaj.org/article/033dfeb6ca854516966c1a66026f40c62021-01-01T00:00:00Zhttps://www.dovepress.com/platinum-nanoparticles-enhance-exosome-release-in-human-lung-epithelia-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sangiliyandi Gurunathan, Min-Hee Kang, Muniyandi Jeyaraj, Jin-Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaCorrespondence: Sangiliyandi Gurunathan; Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaTel +82 2 450 3687Fax + 82 2 544 4645Email gsangiliyandi@yahoo.com; jhkim541@konkuk.ac.krBackground: Several studies have demonstrated various molecular mechanisms involved in the biogenesis and release of exosomes. However, how external stimuli, such as platinum nanoparticles (PtNPs), induces the biogenesis and release of exosomes remains unclear. To address this, PtNPs were synthesized using lutein to examine their effect on the biogenesis and release of exosomes in human lung epithelial adenocarcinoma cancer cells (A549).Methods: The size and concentration of isolated exosomes were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis system (NTA). Morphology and structure of exosomes were examined using scanning electron microscopy and transmission electron microscopy (TEM), respectively. Quantification of exosomes were analyzed by EXOCETTM assay and fluorescence polarization (FP). The expression of typical markers of exosomes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results: A549 cells cultured with PtNPs enhance exosome secretion by altering various physiological processes. Interestingly, A549 cells treated with PtNPs increases total protein concentration, biogenesis and release of exosomes associated with PtNPs-induced oxidative stress. GW4869 inhibits PtNPs induced biogenesis and release of exosomes and also acetylcholinesterase (AChE), neutral sphingomyelinase activity (n-SMase), and exosome counts. A549 cells pre-treated with N-acetylcysteine (NAC) significantly inhibited PtNPs induced exosome biogenesis and release. These findings confirmed that PtNPs-induced exosome release was due to the induction of oxidative stress and the ceramide pathway. These factors enhanced exosome biogenesis and release and may be useful in understanding the mechanism of exosome formation, release, and function.Conclusion: PtNPs provide a promising agent to increase exosome production in A549 cells. These findings offer novel strategies for enhancing exosome release, which can be applied in the treatment and prevention of cancer. Importantly, this is the first study, to our knowledge, showing that PtNPs stimulate exosome biogenesis by inducing oxidative stress and the ceramide pathway.Keywords: exosome, platinum nanoparticle, cytotoxicity, oxidative stress, acetylcholinesterase activity, neutral sphingomyelinase activityGurunathan SKang MHJeyaraj MKim JHDove Medical Pressarticleexosomeplatinum nanoparticlecytotoxicityoxidative stressacetylcholinesterase activityneutral sphingomyelinase activityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 515-538 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exosome platinum nanoparticle cytotoxicity oxidative stress acetylcholinesterase activity neutral sphingomyelinase activity Medicine (General) R5-920
spellingShingle	exosome platinum nanoparticle cytotoxicity oxidative stress acetylcholinesterase activity neutral sphingomyelinase activity Medicine (General) R5-920 Gurunathan S Kang MH Jeyaraj M Kim JH Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players
description	Sangiliyandi Gurunathan, Min-Hee Kang, Muniyandi Jeyaraj, Jin-Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaCorrespondence: Sangiliyandi Gurunathan; Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, KoreaTel +82 2 450 3687Fax + 82 2 544 4645Email gsangiliyandi@yahoo.com; jhkim541@konkuk.ac.krBackground: Several studies have demonstrated various molecular mechanisms involved in the biogenesis and release of exosomes. However, how external stimuli, such as platinum nanoparticles (PtNPs), induces the biogenesis and release of exosomes remains unclear. To address this, PtNPs were synthesized using lutein to examine their effect on the biogenesis and release of exosomes in human lung epithelial adenocarcinoma cancer cells (A549).Methods: The size and concentration of isolated exosomes were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis system (NTA). Morphology and structure of exosomes were examined using scanning electron microscopy and transmission electron microscopy (TEM), respectively. Quantification of exosomes were analyzed by EXOCETTM assay and fluorescence polarization (FP). The expression of typical markers of exosomes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results: A549 cells cultured with PtNPs enhance exosome secretion by altering various physiological processes. Interestingly, A549 cells treated with PtNPs increases total protein concentration, biogenesis and release of exosomes associated with PtNPs-induced oxidative stress. GW4869 inhibits PtNPs induced biogenesis and release of exosomes and also acetylcholinesterase (AChE), neutral sphingomyelinase activity (n-SMase), and exosome counts. A549 cells pre-treated with N-acetylcysteine (NAC) significantly inhibited PtNPs induced exosome biogenesis and release. These findings confirmed that PtNPs-induced exosome release was due to the induction of oxidative stress and the ceramide pathway. These factors enhanced exosome biogenesis and release and may be useful in understanding the mechanism of exosome formation, release, and function.Conclusion: PtNPs provide a promising agent to increase exosome production in A549 cells. These findings offer novel strategies for enhancing exosome release, which can be applied in the treatment and prevention of cancer. Importantly, this is the first study, to our knowledge, showing that PtNPs stimulate exosome biogenesis by inducing oxidative stress and the ceramide pathway.Keywords: exosome, platinum nanoparticle, cytotoxicity, oxidative stress, acetylcholinesterase activity, neutral sphingomyelinase activity
format	article
author	Gurunathan S Kang MH Jeyaraj M Kim JH
author_facet	Gurunathan S Kang MH Jeyaraj M Kim JH
author_sort	Gurunathan S
title	Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players
title_short	Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players
title_full	Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players
title_fullStr	Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players
title_full_unstemmed	Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players
title_sort	platinum nanoparticles enhance exosome release in human lung epithelial adenocarcinoma cancer cells (a549): oxidative stress and the ceramide pathway are key players
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/033dfeb6ca854516966c1a66026f40c6
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Platinum Nanoparticles Enhance Exosome Release in Human Lung Epithelial Adenocarcinoma Cancer Cells (A549): Oxidative Stress and the Ceramide Pathway are Key Players

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