Cell-penetrating d-Isomer Peptides of p53 C-terminus: Long-term Inhibitory Effect on the Growth of Bladder Cancer

Daiji Araki, Kentaro Takayama, Miyabi Inoue, Toyohiko Watanabe, Hiromi Kumon, Shiroh Futaki, Hideki Matsui, Kazuhito Tomizawa

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objectives: To investigate whether a single application of the membrane-permeable d-isomer of the p53 C-terminus connected with a retro-inverso version of the NH2-terminal 20-amino acid peptide of the influenza virus hemagglutinin-2 protein (riHA2) inhibited the growth of bladder cancer cells. The transduction of p53 using poly-arginine is useful for targeting and suppressing the growth of bladder cancer cells. However, the protein's intracellular half-life is short, and repeated application is necessary to achieve an anti-tumor effect. Methods: The p53 carboxyl-terminal peptides covalently coupled with cell-penetrating peptides were synthesized with d- or l-amino acids. Moreover, the peptides were connected with riHA2 by a disulfide bridge. Human bladder cancer cell lines were incubated with each peptide and cell viability was assessed with the WST assay. Apoptotic cells were confirmed by Hoechst and active capase-3 staining. The p53 peptides were injected into severe combined immunodeficiency disease mice transplanted with J82 cells to investigate their anti-tumor effect on bladder tumors. A survival curve was plotted using the Kaplan-Meier method. Results: A single application of cell-penetrating d-isomer peptides of the p53 C-terminus connected with riHA2 (d11R-p53C′-riHA2 and dFHV-p53C′-riHA2) inhibited the growth and induced the apoptosis of bladder cancer cells. The tumor-bearing mice treated only with vehicle had a mean survival time of 12 days, whereas treatment with d11R-p53C′-riHA2 resulted in a long-term survival rate of 50%. Conclusions: Peptide transduction therapy using the d-isomer p53 C-terminal peptide with riHA2 may be an innovative method for the treatment of bladder cancer.

Original languageEnglish
Pages (from-to)813-819
Number of pages7
JournalUrology
Volume75
Issue number4
DOIs
Publication statusPublished - Apr 2010

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Urinary Bladder Neoplasms
Peptides
Growth
Cell-Penetrating Peptides
Amino Acids
Severe Combined Immunodeficiency
Neoplasms
Hemagglutinins
polypeptide C
Orthomyxoviridae
Disulfides
Half-Life
Arginine
Cell Survival
Proteins
Apoptosis
Staining and Labeling
Cell Line
Membranes
Survival

ASJC Scopus subject areas

  • Urology

Cite this

Cell-penetrating d-Isomer Peptides of p53 C-terminus : Long-term Inhibitory Effect on the Growth of Bladder Cancer. / Araki, Daiji; Takayama, Kentaro; Inoue, Miyabi; Watanabe, Toyohiko; Kumon, Hiromi; Futaki, Shiroh; Matsui, Hideki; Tomizawa, Kazuhito.

In: Urology, Vol. 75, No. 4, 04.2010, p. 813-819.

Research output: Contribution to journalArticle

Araki, D, Takayama, K, Inoue, M, Watanabe, T, Kumon, H, Futaki, S, Matsui, H & Tomizawa, K 2010, 'Cell-penetrating d-Isomer Peptides of p53 C-terminus: Long-term Inhibitory Effect on the Growth of Bladder Cancer', Urology, vol. 75, no. 4, pp. 813-819. https://doi.org/10.1016/j.urology.2009.10.002
Araki, Daiji ; Takayama, Kentaro ; Inoue, Miyabi ; Watanabe, Toyohiko ; Kumon, Hiromi ; Futaki, Shiroh ; Matsui, Hideki ; Tomizawa, Kazuhito. / Cell-penetrating d-Isomer Peptides of p53 C-terminus : Long-term Inhibitory Effect on the Growth of Bladder Cancer. In: Urology. 2010 ; Vol. 75, No. 4. pp. 813-819.
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AU - Araki, Daiji

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AU - Watanabe, Toyohiko

AU - Kumon, Hiromi

AU - Futaki, Shiroh

AU - Matsui, Hideki

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