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

doi:10.1016/j.biomaterials.2012.09.003

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 journal › Article › peer-review

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 language	English
Pages (from-to)	9061-9069
Number of pages	9
Journal	Biomaterials
Volume	33
Issue number	35
DOIs	https://doi.org/10.1016/j.biomaterials.2012.09.003
Publication status	Published - 2012 Dec
Externally published	Yes

Keywords

Apoptosis
Brain
Cell proliferation
Drug delivery
Peptide
Protein transduction

ASJC Scopus subject areas

Bioengineering
Ceramics and Composites
Biophysics
Biomaterials
Mechanics of Materials

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.biomaterials.2012.09.003

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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

Ueda, Y, Wei, FY, Hide, TI, Michiue, H, Takayama, K, Kaitsuka, T, Nakamura, H, Makino, K, Kuratsu, JI, 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, vol. 33, no. 35, pp. 9061-9069. https://doi.org/10.1016/j.biomaterials.2012.09.003

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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 = "Apoptosis, Brain, Cell proliferation, Drug delivery, Peptide, Protein transduction",

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

note = "Funding Information: We thank N. Maeda for technical assistance. This work was supported by a Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Japan Society for the Promotion of Science (JSPS) through its “Funding Program for Next Generation World-Leading Researchers”. ",

year = "2012",

month = dec,

doi = "10.1016/j.biomaterials.2012.09.003",

language = "English",

volume = "33",

pages = "9061--9069",

journal = "Biomaterials",

issn = "0142-9612",

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T1 - Induction of autophagic cell death of glioma-initiating cells by cell-penetrating d-isomer peptides consisting of Pas and the p53 C-terminus

AU - Ueda, Yutaka

AU - Wei, Fan Yan

AU - Hide, Taku Ichiro

AU - Michiue, Hiroyuki

AU - Takayama, Kentaro

AU - Kaitsuka, Taku

AU - Nakamura, Hideo

AU - Makino, Keishi

AU - Kuratsu, Jun Ichi

AU - Futaki, Shiroh

AU - Tomizawa, Kazuhito

N1 - Funding Information: We thank N. Maeda for technical assistance. This work was supported by a Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Japan Society for the Promotion of Science (JSPS) through its “Funding Program for Next Generation World-Leading Researchers”.

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Brain

KW - Cell proliferation

KW - Drug delivery

KW - Peptide

KW - Protein transduction

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M3 - Article

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AN - SCOPUS:84867142583

SN - 0142-9612

VL - 33

SP - 9061

EP - 9069

JO - Biomaterials

JF - Biomaterials

IS - 35

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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