| RRC ID |
44067
|
| 著者 |
Ueda Y, Wei FY, Hide T, Michiue H, Takayama K, Kaitsuka T, Nakamura H, Makino K, Kuratsu J, Futaki S, Tomizawa K.
|
| タイトル |
Induction of autophagic cell death of glioma-initiating cells by cell-penetrating D-isomer peptides consisting of Pas and the p53 C-terminus.
|
| ジャーナル |
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.
|
| 巻・号 |
33(35)
|
| ページ |
9061-9
|
| 公開日 |
2012-12-1
|
| 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 |
10.317
|
| 引用数 |
18
|
|
WOS 分野
|
ENGINEERING, BIOMEDICAL
MATERIALS SCIENCE, BIOMATERIALS
|
| リソース情報 |
| ヒト・動物細胞 |
Atg5^(+/+)MEF(RCB2710)
Atg5^(-/-)MEF(RCB2711) |
