Figure 3
From: Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres
Arsenic trioxide inhibits Hedgehog and Notch pathway target gene expression. A) Quantitative PCR analysis revealed that ATO significantly inhibited transcript levels of the Hedgehog pathway target gene PTCH1b at 5 μM in all 3 glioblastoma neurosphere lines compared to vehicle treatment, and in 2 lines after 2.5 μM ATO. ATO also significantly inhibited another Hedgehog pathway target N-Myc in 2 lines at 5 μM, in all 3 glioblastoma neurosphere lines at 2.5 μM, and in 2 lines at 1 μM. GLI2, a 3rd Hedgehog pathway target, was significantly inhibited in all 3 lines at 5 μM ATO, in 1 line at 2.5 μM ATO, and in 2 lines at 1 μM ATO. B) ATO also significantly inhibited expression of the Notch target HES1 as compared to vehicle treatment in HSR-GBM1 and 040622 cells, but not in 040821. HES5 and HEY1 transcript levels were also reduced in all 3 glioblastoma neurosphere lines following 2.5 μM ATO treatment, but a non-significant paradoxical increase was seen at the higher 5 μM dose. C) ATO inhibited HES1 and HES5 protein expression in all 3 glioblastoma neurosphere lines at 5 μM, compared to vehicle treatment.