Assessing the Effects of ONC206, ONC212, and Thymoquinone on Medulloblastoma and Neuroblastoma Cell Models

Abstract

Medulloblastoma (MB) and Neuroblastoma (NB) are among the most aggressive central and peripheral nervous system tumors, respectively. They remain clinically challenging due to their high recurrence rates, resistance to therapy, and long-term toxicities as side effects of current treatment protocols. This study assesses the effects of ONC206 and ONC212, two next generation imipridones, in addition to thymoquinone (TQ), a naturally derived therapeutic compound, on MB (D556 Med) and NB (SK-N-SH) cell models. Antiproliferative and cytotoxic properties were investigated using MTT and Trypan Blue assays, while migratory and stemness potential were examined through wound healing and sphere formation assays. ONC206 and ONC212 significantly reduced the proliferation and viability of both MB and NB cells in a dose dependent manner, with ONC212 exhibiting promising potency at nanomolar concentrations. TQ also displayed cytotoxic activity at higher micromolar concentrations. Migration assays demonstrated that ONC206 and TQ inhibited NB cell migration, whereas no significant effect was measured in MB cells. Preliminary sphere formation experiments suggested potential suppression of stem-like properties for all three compounds. These results provide evidence for the therapeutic potential of ONC206, ONC212, and TQ in MB and NB, with ONC212 emerging as the most potent candidate. Further investigations are needed to validate these observations and assess the translational potential of these outcomes into clinical settings.