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Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma by Maximilian Pruss; Annika Dwucet; Mine Tanriover; Michal Hlavac; Richard Eric Kast; Klaus-Michael Debatin; Christian Rainer Wirtz; Marc-Eric Halatsch; Markus David Siegelin; Mike-Andrew Westhoff; Georg Karpel-Massler is a Medicine article available to read on EtoBox.
What is Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma about?
## Background Dysregulation of the metabolome is a hallmark of primary brain malignancies. In this work we examined whether metabolic reprogramming through a multi-targeting approach causes enhanced anti-cancer activity in glioblastoma. ## Methods Preclinical testing of a combined treatment with ONC201/TIC10 and 2-Deoxyglucose was performed in established and primary-cultured glioblastoma cells. Extracellular flux analysis was used to determine real-time effects on OXPHOS and glycolysis. Respiratory chain complexes were analysed by western blotting. Biological effects on tumour formation were tested on the chorioallantoic membrane (CAM). ## Results ONC201/TIC10 impairs mitochondrial respiration accompanied by an increase of glycolysis. When combined with 2-Deoxyglucose, ONC201/TIC10 induces a state of energy depletion as outlined by a significant decrease in ATP levels and a hypo-phosphorylative state. As a result, synergistic anti-proliferative and anti-migratory effects were observed among a broad panel of different glioblastoma cells. In addition, this combinatorial approach significantly impaired tumour formation on the CAM. ## Conclusion Treatment with ONC201/TIC10 and 2-Deoxy
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- Author
- Maximilian Pruss; Annika Dwucet; Mine Tanriover; Michal Hlavac; Richard Eric Kast; Klaus-Michael Debatin; Christian Rainer Wirtz; Marc-Eric Halatsch; Markus David Siegelin; Mike-Andrew Westhoff; Georg Karpel-Massler
- Publisher
- Nature Publishing Group; Springer Science and Business Media LLC; Society for Mining, Metallurgy and Exploration Inc. (ISSN 0007-0920)
- Published
- 2020
- Language
- EN
- Field
- Medicine (Health Sciences)