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Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition

Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, th...

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Autores principales: Morais, Catarina M., Cardoso, Ana M., Araújo, Ana Rita D., Reis, Ana, Domingues, Pedro, Domingues, Maria Rosário M., de Lima, Maria C. Pedroso, Jurado, Amália S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654881/
https://www.ncbi.nlm.nih.gov/pubmed/36361811
http://dx.doi.org/10.3390/ijms232113014
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author Morais, Catarina M.
Cardoso, Ana M.
Araújo, Ana Rita D.
Reis, Ana
Domingues, Pedro
Domingues, Maria Rosário M.
de Lima, Maria C. Pedroso
Jurado, Amália S.
author_facet Morais, Catarina M.
Cardoso, Ana M.
Araújo, Ana Rita D.
Reis, Ana
Domingues, Pedro
Domingues, Maria Rosário M.
de Lima, Maria C. Pedroso
Jurado, Amália S.
author_sort Morais, Catarina M.
collection PubMed
description Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.
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spelling pubmed-96548812022-11-15 Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition Morais, Catarina M. Cardoso, Ana M. Araújo, Ana Rita D. Reis, Ana Domingues, Pedro Domingues, Maria Rosário M. de Lima, Maria C. Pedroso Jurado, Amália S. Int J Mol Sci Article Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic. MDPI 2022-10-27 /pmc/articles/PMC9654881/ /pubmed/36361811 http://dx.doi.org/10.3390/ijms232113014 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morais, Catarina M.
Cardoso, Ana M.
Araújo, Ana Rita D.
Reis, Ana
Domingues, Pedro
Domingues, Maria Rosário M.
de Lima, Maria C. Pedroso
Jurado, Amália S.
Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
title Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
title_full Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
title_fullStr Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
title_full_unstemmed Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
title_short Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
title_sort stearoyl coa desaturase-1 silencing in glioblastoma cells: phospholipid remodeling and cytotoxicity enhanced upon autophagy inhibition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654881/
https://www.ncbi.nlm.nih.gov/pubmed/36361811
http://dx.doi.org/10.3390/ijms232113014
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