Arsenic trioxide sensitizes glioblastoma to a Myc inhibitor

Yayoi Yoshimura, Akihiko Shiino, Kazue Muraki, Tadateru Fukami, Shigeki Yamada, Takeshi Satow, Miyuki Fukuda, Masaaki Saiki, Masato Hojo, Susumu Miyamoto, Nobuyuki Onishi, Hideyuki Saya, Toshiro Inubushi, Kazuhiko Nozaki, Kenji Tanigaki

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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<sup>-/-</sup> 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.

Original languageEnglish
Article numbere0128288
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - 2015 Jun 3

Fingerprint

Glioblastoma
arsenic
Neoplastic Stem Cells
neoplasms
Stem cells
stems
stem cells
Neural Stem Cells
therapeutics
Heterografts
cell differentiation
cooperatives
Tumors
animal models
Growth
arsenic trioxide
cells
Cell Differentiation
Therapeutics
Recurrence

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Yoshimura, Y., Shiino, A., Muraki, K., Fukami, T., Yamada, S., Satow, T., ... Tanigaki, K. (2015). Arsenic trioxide sensitizes glioblastoma to a Myc inhibitor. PLoS One, 10(6), [e0128288]. https://doi.org/10.1371/journal.pone.0128288

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.

In: PLoS One, Vol. 10, No. 6, e0128288, 03.06.2015.

Research output: Contribution to journalArticle

Yoshimura, Y, Shiino, A, Muraki, K, Fukami, T, Yamada, S, Satow, T, Fukuda, M, Saiki, M, Hojo, M, Miyamoto, S, Onishi, N, Saya, H, Inubushi, T, Nozaki, K & Tanigaki, K 2015, 'Arsenic trioxide sensitizes glioblastoma to a Myc inhibitor', PLoS One, vol. 10, no. 6, e0128288. https://doi.org/10.1371/journal.pone.0128288
Yoshimura Y, Shiino A, Muraki K, Fukami T, Yamada S, Satow T et al. Arsenic trioxide sensitizes glioblastoma to a Myc inhibitor. PLoS One. 2015 Jun 3;10(6). e0128288. https://doi.org/10.1371/journal.pone.0128288
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. In: PLoS One. 2015 ; Vol. 10, No. 6.
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