TY - JOUR
T1 - Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres
AU - Ding, Dacheng
AU - Lim, Kah Suan
AU - Eberhart, Charles G.
N1 - Publisher Copyright:
© 2014 Ding et al.; licensee BioMed Central Ltd.
PY - 2014/1/27
Y1 - 2014/1/27
N2 - Background: Notch and Hedgehog signaling have been implicated in the pathogenesis and stem-like characteristics of glioblastomas, and inhibitors of the pathways have been suggested as new therapies for these aggressive tumors. It has also been reported that targeting both pathways simultaneously can be advantageous in treating glioblastoma neurospheres, but this is difficult to achieve in vivo using multiple agents. Since arsenic trioxide has been shown to inhibit both Notch and Hedgehog in some solid tumors, we examined its effects on these pathways and on stem cell phenotype in glioblastoma. Results: We found that arsenic trioxide suppresses proliferation and promotes apoptosis in three stem-like glioblastoma neurospheres lines, while inhibiting Notch and Hedgehog target genes. Importantly, arsenic trioxide markedly reduced clonogenic capacity of the tumor neurospheres, and the stem-like CD133-positive fraction was also diminished along with expression of the stem cell markers SOX2 and CD133. Conclusions: Our results suggest that arsenic trioxide may be effective in targeting stem-like glioblastoma cells in patients by inhibiting Notch and Hedgehog activity.
AB - Background: Notch and Hedgehog signaling have been implicated in the pathogenesis and stem-like characteristics of glioblastomas, and inhibitors of the pathways have been suggested as new therapies for these aggressive tumors. It has also been reported that targeting both pathways simultaneously can be advantageous in treating glioblastoma neurospheres, but this is difficult to achieve in vivo using multiple agents. Since arsenic trioxide has been shown to inhibit both Notch and Hedgehog in some solid tumors, we examined its effects on these pathways and on stem cell phenotype in glioblastoma. Results: We found that arsenic trioxide suppresses proliferation and promotes apoptosis in three stem-like glioblastoma neurospheres lines, while inhibiting Notch and Hedgehog target genes. Importantly, arsenic trioxide markedly reduced clonogenic capacity of the tumor neurospheres, and the stem-like CD133-positive fraction was also diminished along with expression of the stem cell markers SOX2 and CD133. Conclusions: Our results suggest that arsenic trioxide may be effective in targeting stem-like glioblastoma cells in patients by inhibiting Notch and Hedgehog activity.
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U2 - 10.1186/2051-5960-2-31
DO - 10.1186/2051-5960-2-31
M3 - Article
C2 - 24685274
AN - SCOPUS:84914669542
SN - 2051-5960
VL - 2
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 31
ER -