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.