Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor

Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation...

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Main Authors:	Yoshimura, Yayoi, Shiino, Akihiko, Muraki, Kazue, Fukami, Tadateru, Yamada, Shigeki, Satow, Takeshi, Fukuda, Miyuki, Saiki, Masaaki, Hojo, Masato, Miyamoto, Susumu, Onishi, Nobuyuki, Saya, Hideyuki, Inubushi, Toshiro, Nozaki, Kazuhiko, Tanigaki, Kenji
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454553/

id	pubmed-4454553
recordtype	oai_dc
spelling	pubmed-44545532015-06-09 Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor Yoshimura, Yayoi Shiino, Akihiko Muraki, Kazue Fukami, Tadateru Yamada, Shigeki Satow, Takeshi Fukuda, Miyuki Saiki, Masaaki Hojo, Masato Miyamoto, Susumu Onishi, Nobuyuki Saya, Hideyuki Inubushi, Toshiro Nozaki, Kazuhiko Tanigaki, Kenji Research Article Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC) of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs) than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM. Public Library of Science 2015-06-03 /pmc/articles/PMC4454553/ /pubmed/26038891 http://dx.doi.org/10.1371/journal.pone.0128288 Text en © 2015 Yoshimura et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yoshimura, Yayoi Shiino, Akihiko Muraki, Kazue Fukami, Tadateru Yamada, Shigeki Satow, Takeshi Fukuda, Miyuki Saiki, Masaaki Hojo, Masato Miyamoto, Susumu Onishi, Nobuyuki Saya, Hideyuki Inubushi, Toshiro Nozaki, Kazuhiko Tanigaki, Kenji
spellingShingle	Yoshimura, Yayoi Shiino, Akihiko Muraki, Kazue Fukami, Tadateru Yamada, Shigeki Satow, Takeshi Fukuda, Miyuki Saiki, Masaaki Hojo, Masato Miyamoto, Susumu Onishi, Nobuyuki Saya, Hideyuki Inubushi, Toshiro Nozaki, Kazuhiko Tanigaki, Kenji Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor
author_facet	Yoshimura, Yayoi Shiino, Akihiko Muraki, Kazue Fukami, Tadateru Yamada, Shigeki Satow, Takeshi Fukuda, Miyuki Saiki, Masaaki Hojo, Masato Miyamoto, Susumu Onishi, Nobuyuki Saya, Hideyuki Inubushi, Toshiro Nozaki, Kazuhiko Tanigaki, Kenji
author_sort	Yoshimura, Yayoi
title	Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor
title_short	Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor
title_full	Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor
title_fullStr	Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor
title_full_unstemmed	Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor
title_sort	arsenic trioxide sensitizes glioblastoma to a myc inhibitor
description	Glioblastoma multiforme (GBM) is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC) of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs) than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454553/
_version_	1613231470537605120

Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor

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