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 journalArticlepeer-review

    24 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 - Dec 2012

    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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