TY - JOUR
T1 - Arsenic trioxide sensitizes glioblastoma to a Myc inhibitor
AU - Yoshimura, Yayoi
AU - Shiino, Akihiko
AU - Muraki, Kazue
AU - Fukami, Tadateru
AU - Yamada, Shigeki
AU - Satow, Takeshi
AU - Fukuda, Miyuki
AU - Saiki, Masaaki
AU - Hojo, Masato
AU - Miyamoto, Susumu
AU - Onishi, Nobuyuki
AU - Saya, Hideyuki
AU - Inubushi, Toshiro
AU - Nozaki, Kazuhiko
AU - Tanigaki, Kenji
N1 - Funding Information:
This work was supported by Sagawa Foundation (K.T.) and Yasuda Medical Foundation (K.T.).
Publisher Copyright:
© 2015 Yoshimura et al. 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 credited.
PY - 2015/6/3
Y1 - 2015/6/3
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0128288
DO - 10.1371/journal.pone.0128288
M3 - Article
C2 - 26038891
AN - SCOPUS:84932634326
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 6
M1 - e0128288
ER -
