2010年4月
Cell-penetrating D-Isomer Peptides of p53 C-terminus: Long-term Inhibitory Effect on the Growth of Bladder Cancer
UROLOGY
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- 巻
- 75
- 号
- 4
- 開始ページ
- 813
- 終了ページ
- 819
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.urology.2009.10.002
- 出版者・発行元
- ELSEVIER SCIENCE INC
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 NH(2)-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. UROLOGY 75: 813-819, 2010. (C) 2010 Elsevier Inc.
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. UROLOGY 75: 813-819, 2010. (C) 2010 Elsevier Inc.
- リンク情報
- ID情報
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- DOI : 10.1016/j.urology.2009.10.002
- ISSN : 0090-4295
- PubMed ID : 19963248
- Web of Science ID : WOS:000276258300010