ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression

The purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in h...

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Autores principales:	Annika Dwucet, Maximilian Pruss, Qiyu Cao, Mine Tanriover, Varun V. Prabhu, Joshua E. Allen, Aurelia Peraud, Mike-Andrew Westhoff, Markus D. Siegelin, Christian Rainer Wirtz, Georg Karpel-Massler
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	medulloblastoma ONC201/TIC10 2-Deoxyglucose seahorse metabolism Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2b45188c50c34313bc4b235cbf25243c
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spelling	oai:doaj.org-article:2b45188c50c34313bc4b235cbf25243c2021-12-01T07:04:49ZONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression2296-634X10.3389/fcell.2021.734699https://doaj.org/article/2b45188c50c34313bc4b235cbf25243c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.734699/fullhttps://doaj.org/toc/2296-634XThe purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in high and low c-myc-expressing medulloblastoma cells. Our data show that treatment with the imipridone ONC201/TIC10 leads to a significant inihibitory effect on the cellular viability of different medulloblastoma cells independent of c-myc expression. This effect is enhanced by glucose starvation. While ONC201/TIC10 decreases the oxidative consumption rates in D458 (c-myc high) and DAOY (c-myc low) cells extracellular acidification rates experienced an increase in D458 and a decrease in DAOY cells. Combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose led to a synergistic inhibitory effect on the cellular viability of medulloblastoma cells including spheroid models. In conclusion, our data suggest that ONC201/TIC10 has a profound anti-proliferative activity against medulloblastoma cells independent of c-myc expression. Metabolic targeting of medulloblastoma cells by ONC201/TIC10 can be significantly enhanced by an additional treatment with the glycolysis inhibitor 2-Deoxyglucose. Further investigations are warranted.Annika DwucetMaximilian PrussQiyu CaoMine TanrioverVarun V. PrabhuJoshua E. AllenAurelia PeraudMike-Andrew WesthoffMarkus D. SiegelinChristian Rainer WirtzGeorg Karpel-MasslerFrontiers Media S.A.articlemedulloblastomaONC201/TIC102-DeoxyglucoseseahorsemetabolismBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	medulloblastoma ONC201/TIC10 2-Deoxyglucose seahorse metabolism Biology (General) QH301-705.5
spellingShingle	medulloblastoma ONC201/TIC10 2-Deoxyglucose seahorse metabolism Biology (General) QH301-705.5 Annika Dwucet Maximilian Pruss Qiyu Cao Mine Tanriover Varun V. Prabhu Joshua E. Allen Aurelia Peraud Mike-Andrew Westhoff Markus D. Siegelin Christian Rainer Wirtz Georg Karpel-Massler ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
description	The purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in high and low c-myc-expressing medulloblastoma cells. Our data show that treatment with the imipridone ONC201/TIC10 leads to a significant inihibitory effect on the cellular viability of different medulloblastoma cells independent of c-myc expression. This effect is enhanced by glucose starvation. While ONC201/TIC10 decreases the oxidative consumption rates in D458 (c-myc high) and DAOY (c-myc low) cells extracellular acidification rates experienced an increase in D458 and a decrease in DAOY cells. Combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose led to a synergistic inhibitory effect on the cellular viability of medulloblastoma cells including spheroid models. In conclusion, our data suggest that ONC201/TIC10 has a profound anti-proliferative activity against medulloblastoma cells independent of c-myc expression. Metabolic targeting of medulloblastoma cells by ONC201/TIC10 can be significantly enhanced by an additional treatment with the glycolysis inhibitor 2-Deoxyglucose. Further investigations are warranted.
format	article
author	Annika Dwucet Maximilian Pruss Qiyu Cao Mine Tanriover Varun V. Prabhu Joshua E. Allen Aurelia Peraud Mike-Andrew Westhoff Markus D. Siegelin Christian Rainer Wirtz Georg Karpel-Massler
author_facet	Annika Dwucet Maximilian Pruss Qiyu Cao Mine Tanriover Varun V. Prabhu Joshua E. Allen Aurelia Peraud Mike-Andrew Westhoff Markus D. Siegelin Christian Rainer Wirtz Georg Karpel-Massler
author_sort	Annika Dwucet
title	ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
title_short	ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
title_full	ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
title_fullStr	ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
title_full_unstemmed	ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression
title_sort	onc201/tic10 is empowered by 2-deoxyglucose and causes metabolic reprogramming in medulloblastoma cells in vitro independent of c-myc expression
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2b45188c50c34313bc4b235cbf25243c
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ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression

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