title: Arsenic trioxide depletes cancer stem-like cells and inhibits repopulation of neurosphere derived from glioblastoma by downregulation of Notch pathway.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ji
authors.forename: Huailei
authors.initials: H
authors.lastname: Liu
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Liu
authors.forename: Dayong
authors.initials: D
authors.lastname: Han
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
authors.forename: Changbin
authors.initials: C
authors.lastname: Shi
authors.forename: Chunlei
authors.initials: C
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.forename: Huadong
authors.initials: H
authors.lastname: Li
authors.forename: Yunke
authors.initials: Y
authors.lastname: Bi
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010087:Oxides / Q000633:toxicity*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D000970:Antineoplastic Agents; D000077237:Arsenic Trioxide; D001152:Arsenicals; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D010087:Oxides; D051057:Proto-Oncogene Proteins c-akt; D051880:Receptors, Notch; D050796:STAT3 Transcription Factor; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human