Arsenic trioxide depletes cancer stem-like cells and inhibits repopulation of neurosphere derived from glioblastoma by downregulation of Notch pathway

- ATO has inhibitory effect on cancer stem-like cells of glioblastoma.
- ATO blocks Notch and inhibits neurosphere recovery and secondary formation.
- NICD protects apoptosis and neurosphere cultures from ATO treatment.
- GSI enhanced therapy of ATO in both GBM cell lines and neurosphere cultures.
- ATO inhibits phosphorylation of AKT and STAT3 through Notch signaling blockade.

Notch signaling has been demonstrated to have a central role in cancer stem-like cells (CSLCs) in glioblastoma multiforme (GBM). We have recently demonstrated the inhibitory effect of arsenic trioxide (ATO) on CSLCs in glioblastoma cell lines. In this study we used neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after ATO treatment. Our results provided strong evidence that ATO depleted CSLCs in GBM, and inhibited neurosphere recovery and secondary neurosphere formation. ATO inhibited the phosphorylation and activation of AKT and STAT3 through Notch signaling blockade. These data show that the ATO is a promising new approach to decrease glioblastoma proliferation and recurrence by downregulation of Notch pathway.