RRC ID 44067
Author Ueda Y, Wei FY, Hide T, Michiue H, Takayama K, Kaitsuka T, Nakamura H, Makino K, Kuratsu J, Futaki S, Tomizawa K.
Title Induction of autophagic cell death of glioma-initiating cells by cell-penetrating D-isomer peptides consisting of Pas and the p53 C-terminus.
Journal Biomaterials
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.
Volume 33(35)
Pages 9061-9
Published 2012-12
DOI 10.1016/j.biomaterials.2012.09.003
PII S0142-9612(12)00979-9
PMID 23006589
MeSH Animals Apoptosis / drug effects Autophagy / drug effects* Autophagy / physiology* Blotting, Western Brain / drug effects Brain / pathology Brain Neoplasms / drug therapy Brain Neoplasms / pathology Cell Line, Tumor Cell Proliferation / drug effects Cell-Penetrating Peptides / chemistry* Cell-Penetrating Peptides / pharmacology Drug Delivery Systems / methods Female Glioma / pathology* Humans Immunohistochemistry In Situ Nick-End Labeling Mice Mice, Nude Microscopy, Electron, Transmission Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / pathology Signal Transduction Transfection Tumor Suppressor Protein p53 / chemistry
IF 10.273
Times Cited 18
Human and Animal Cells