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The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines

Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LB...

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Autores principales: Krętowski, Rafał, Kusaczuk, Magdalena, Naumowicz, Monika, Kotyńska, Joanna, Szynaka, Beata, Cechowska-Pasko, Marzanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575712/
https://www.ncbi.nlm.nih.gov/pubmed/28825685
http://dx.doi.org/10.3390/nano7080230
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author Krętowski, Rafał
Kusaczuk, Magdalena
Naumowicz, Monika
Kotyńska, Joanna
Szynaka, Beata
Cechowska-Pasko, Marzanna
author_facet Krętowski, Rafał
Kusaczuk, Magdalena
Naumowicz, Monika
Kotyńska, Joanna
Szynaka, Beata
Cechowska-Pasko, Marzanna
author_sort Krętowski, Rafał
collection PubMed
description Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5–15 nm and 10–20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs. Furthermore, in LBC3 cells treated with 5–15 nm SiNPs we noticed induction of apoptosis and necrosis, while in LN-18 cells only necrosis. The 5–15 nm SiNPs were also found to cause oxidative stress, a loss in mitochondrial membrane potential, and changes in the ultrastructure of the mitochondria in LBC3 cells. Quantitative real-time PCR results showed that in LBC3 cells the mRNA levels of pro-apoptotic genes Bim, Bax, Puma, and Noxa were significantly upregulated. An increase in activity of caspase-9 in these cells was also observed. Moreover, the activation of SiNP-induced autophagy was demonstrated in LBC3 cells as shown by an increase in LC3-II/LC3-I ratio, the upregulation of Atg5 gene and an increase in AVOs-positive cells. In conclusion, this research provides novel information concerning molecular mechanisms of apoptosis and autophagy in LBC3 cells.
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spelling pubmed-55757122017-09-01 The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines Krętowski, Rafał Kusaczuk, Magdalena Naumowicz, Monika Kotyńska, Joanna Szynaka, Beata Cechowska-Pasko, Marzanna Nanomaterials (Basel) Article Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5–15 nm and 10–20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs. Furthermore, in LBC3 cells treated with 5–15 nm SiNPs we noticed induction of apoptosis and necrosis, while in LN-18 cells only necrosis. The 5–15 nm SiNPs were also found to cause oxidative stress, a loss in mitochondrial membrane potential, and changes in the ultrastructure of the mitochondria in LBC3 cells. Quantitative real-time PCR results showed that in LBC3 cells the mRNA levels of pro-apoptotic genes Bim, Bax, Puma, and Noxa were significantly upregulated. An increase in activity of caspase-9 in these cells was also observed. Moreover, the activation of SiNP-induced autophagy was demonstrated in LBC3 cells as shown by an increase in LC3-II/LC3-I ratio, the upregulation of Atg5 gene and an increase in AVOs-positive cells. In conclusion, this research provides novel information concerning molecular mechanisms of apoptosis and autophagy in LBC3 cells. MDPI 2017-08-21 /pmc/articles/PMC5575712/ /pubmed/28825685 http://dx.doi.org/10.3390/nano7080230 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krętowski, Rafał
Kusaczuk, Magdalena
Naumowicz, Monika
Kotyńska, Joanna
Szynaka, Beata
Cechowska-Pasko, Marzanna
The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
title The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
title_full The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
title_fullStr The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
title_full_unstemmed The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
title_short The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines
title_sort effects of silica nanoparticles on apoptosis and autophagy of glioblastoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575712/
https://www.ncbi.nlm.nih.gov/pubmed/28825685
http://dx.doi.org/10.3390/nano7080230
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