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

Paper ID Volume ID Publish Year Pages File Format Full-Text
6601 502 2012 9 PDF Available
Title
Induction of autophagic cell death of glioma-initiating cells by cell-penetrating d-isomer peptides consisting of Pas and the p53 C-terminus
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.

Keywords
Brain; Peptide; Drug delivery; Apoptosis; Cell proliferation; Protein transduction
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Induction of autophagic cell death of glioma-initiating cells by cell-penetrating d-isomer peptides consisting of Pas and the p53 C-terminus
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 35, December 2012, Pages 9061–9069
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us