title: Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres.
abstract: 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.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ding
authors.forename: Kah Suan
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. ceberha@jhmi.edu.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; D010087:Oxides; D051880:Receptors, Notch; D000077237:Arsenic Trioxide