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Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977902/ https://www.ncbi.nlm.nih.gov/pubmed/24685274 http://dx.doi.org/10.1186/2051-5960-2-31 |
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author | Ding, Dacheng Lim, Kah Suan Eberhart, Charles G |
author_facet | Ding, Dacheng Lim, Kah Suan Eberhart, Charles G |
author_sort | Ding, Dacheng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3977902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39779022014-04-08 Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres Ding, Dacheng Lim, Kah Suan Eberhart, Charles G Acta Neuropathol Commun Research 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. BioMed Central 2014-03-31 /pmc/articles/PMC3977902/ /pubmed/24685274 http://dx.doi.org/10.1186/2051-5960-2-31 Text en Copyright © 2014 Ding et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ding, Dacheng Lim, Kah Suan Eberhart, Charles G Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres |
title | Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres |
title_full | Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres |
title_fullStr | Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres |
title_full_unstemmed | Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres |
title_short | Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in glioblastoma neurospheres |
title_sort | arsenic trioxide inhibits hedgehog, notch and stem cell properties in glioblastoma neurospheres |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977902/ https://www.ncbi.nlm.nih.gov/pubmed/24685274 http://dx.doi.org/10.1186/2051-5960-2-31 |
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