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Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells

Simvastatin, a commonly used cholesterol‐lowering drug, inhibits the mevalonate pathway involved in the synthesis of the mitochondrial electron carrier coenzyme Q10 (CoQ10), as well as other bioenergetics substrates. The purpose of this study was to investigate simvastatin exposure on mitochondrial...

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Detalles Bibliográficos
Autores principales: Kuzyk, Crystal L., Anderson, Colin C., Roede, James R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214657/
https://www.ncbi.nlm.nih.gov/pubmed/31917509
http://dx.doi.org/10.1111/cts.12740
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author Kuzyk, Crystal L.
Anderson, Colin C.
Roede, James R.
author_facet Kuzyk, Crystal L.
Anderson, Colin C.
Roede, James R.
author_sort Kuzyk, Crystal L.
collection PubMed
description Simvastatin, a commonly used cholesterol‐lowering drug, inhibits the mevalonate pathway involved in the synthesis of the mitochondrial electron carrier coenzyme Q10 (CoQ10), as well as other bioenergetics substrates. The purpose of this study was to investigate simvastatin exposure on mitochondrial respiration, metabolic fuel preferences, and glucose utilization. We hypothesized that simvastatin at a noncytotoxic dose will impair energy metabolism in human neuroblastoma cells. SK‐N‐AS cells were exposed at acute and chronic time points and evaluated in a Seahorse XF analyzer, revealing decreased mitochondrial and glycolytic parameters. Flow cytometry showed a significant induction of apoptosis in simvastatin‐treated cells at 48 hours. Finally, multiple techniques were used to show that simvastatin‐mediated impairment of bioenergetics is more complex than CoQ10 depletion or hampered glucose uptake. Therefore, the data reported here represent a biphasic hit to mitochondria followed by reduction in glucose and glutamine metabolism in neuroblastoma; adding mechanism to potential pleotropic effects of statins.
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spelling pubmed-72146572020-05-13 Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells Kuzyk, Crystal L. Anderson, Colin C. Roede, James R. Clin Transl Sci Research Simvastatin, a commonly used cholesterol‐lowering drug, inhibits the mevalonate pathway involved in the synthesis of the mitochondrial electron carrier coenzyme Q10 (CoQ10), as well as other bioenergetics substrates. The purpose of this study was to investigate simvastatin exposure on mitochondrial respiration, metabolic fuel preferences, and glucose utilization. We hypothesized that simvastatin at a noncytotoxic dose will impair energy metabolism in human neuroblastoma cells. SK‐N‐AS cells were exposed at acute and chronic time points and evaluated in a Seahorse XF analyzer, revealing decreased mitochondrial and glycolytic parameters. Flow cytometry showed a significant induction of apoptosis in simvastatin‐treated cells at 48 hours. Finally, multiple techniques were used to show that simvastatin‐mediated impairment of bioenergetics is more complex than CoQ10 depletion or hampered glucose uptake. Therefore, the data reported here represent a biphasic hit to mitochondria followed by reduction in glucose and glutamine metabolism in neuroblastoma; adding mechanism to potential pleotropic effects of statins. John Wiley and Sons Inc. 2020-02-06 2020-05 /pmc/articles/PMC7214657/ /pubmed/31917509 http://dx.doi.org/10.1111/cts.12740 Text en © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research
Kuzyk, Crystal L.
Anderson, Colin C.
Roede, James R.
Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells
title Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells
title_full Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells
title_fullStr Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells
title_full_unstemmed Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells
title_short Simvastatin Induces Delayed Apoptosis Through Disruption of Glycolysis and Mitochondrial Impairment in Neuroblastoma Cells
title_sort simvastatin induces delayed apoptosis through disruption of glycolysis and mitochondrial impairment in neuroblastoma cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214657/
https://www.ncbi.nlm.nih.gov/pubmed/31917509
http://dx.doi.org/10.1111/cts.12740
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