Induction of autophagic cell death of glioma-initiating cells by cell-penetrating d-isomer peptides consisting of Pas and the p53 C-terminus

Yutaka Ueda, Fan Yan Wei, Taku Ichiro Hide, Hiroyuki Michiue, Kentaro Takayama, Taku Kaitsuka, Hideo Nakamura, Keishi Makino, Jun Ichi Kuratsu, Shiroh Futaki, Kazuhito Tomizawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and fatal brain tumor. GBM is resistant to chemotherapy and radiation. Recent studies have shown that glioma-initiating cells (GICs), which have characteristics of cancer stem cells, are responsible for the resistance to chemotherapy and radiation and regrowth. No effective therapy for GICs has been developed. Here we showed that d-isomer peptides (dPasFHV-p53C') consisting of a cell-penetrating peptide (FHV), penetration accelerating sequence (Pas) and C-terminus of p53 (p53C') induced the cell death of GICs. dPasFHV-p53C' was effectively transduced into human GICs. The peptides dose-dependently inhibited cell growth and at 3 μM completely blocked the growth of GICs but not embryonic stem cells. Autophagic cell death was observed in the GICs treated with dPasFHV-p53C' but apoptosis was not. dPasFHV without p53C' showed the same effect as dPasFHV-p53C', suggesting Pas to play a critical role in the cell death of GICs. Finally, dPasFHV-p53C' reduced tumor mass in mice transplanted with GICs. Peptide transduction therapy using dPasFHV-p53C' could be a new method for the treatment of GBM.

Original languageEnglish
Pages (from-to)9061-9069
Number of pages9
JournalBiomaterials
Volume33
Issue number35
DOIs
Publication statusPublished - 2012 Dec

Keywords

  • Apoptosis
  • Brain
  • Cell proliferation
  • Drug delivery
  • Peptide
  • Protein transduction

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Ueda, Y., Wei, F. Y., Hide, T. I., Michiue, H., Takayama, K., Kaitsuka, T., Nakamura, H., Makino, K., Kuratsu, J. I., Futaki, S., & Tomizawa, K. (2012). Induction of autophagic cell death of glioma-initiating cells by cell-penetrating d-isomer peptides consisting of Pas and the p53 C-terminus. Biomaterials, 33(35), 9061-9069. https://doi.org/10.1016/j.biomaterials.2012.09.003