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Cen-Penetrating D-IsomerPeptidesofp53C-Terminus: Long-term Inhibitory Effect on the Growth of Bladder Cancer

Research Project

Project/Area Number 20591856
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOkayama University

Principal Investigator

WATANABE Toyohiko  Okayama University, 岡山大学病院, 講師 (30432644)

Co-Investigator(Kenkyū-buntansha) TOMIAZAWA Kazuhito  熊本大学, 大学院・生命科学研究部, 教授 (40274287)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞 / 組織 / 細胞・組織
Research 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.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (11 results)

All 2010 2009 2008

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (3 results)

  • [Journal Article] The future of urodynamics : Non-invasive ultrasound videourodynamics.2010

    • Author(s)
      Ozawa H., Igarashi T., Uematsu K., Watanabe T., Kumon H.
    • Journal Title

      Int J Urol. 17巻

      Pages: 241-249

    • NAID

      10027257485

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chancellor MB. Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment.2010

    • Author(s)
      Watanabe T., Inoue M., Sasaki K., Araki M., Uehara S., Monden K., Saika T., Nasu Y., Kumon H.
    • Journal Title

      BJU International.(Epub ahead of print.)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell-penetrating d-isomer peptides of p53 C-terminus : long-term inhibitory effect on the growth of bladder cancer Urology.2010

    • Author(s)
      Araki D., Takayama K., Inoue M., Watanabe T., Kumon H., Futaki S., Matsui H., Tomizawa K.
    • Journal Title

      75巻

      Pages: 813-819

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell-penetrating d-isomer peptides of p53 C-terminus : long-term inhibitory effect on the growth of bladder cancer2010

    • Author(s)
      荒木大司
    • Journal Title

      Urology

      Volume: 75 Pages: 813-819

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Okayama Urological Research Group. Naftopidil and propiverine hydrochloride for treatment of male lower urinary tract symptoms suggestive of benign prostatic hyperplasia and concomitant overactive bladder : a prospective randomized controlled study.2009

    • Author(s)
      Yokoyama T., Uematsu K., Watanabe T., Sasaki K., Kumon H., Nagai A.
    • Journal Title

      Scand J Urol Nephrol. 43巻

      Pages: 307-314

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experimental and clinical studies on fluoroquinolone-insusceptible Escherichia coli isolated from patients with urinary tract infections from 1994 to 2007.2009

    • Author(s)
      Wada K., Kariyama R., Mitsuhata R., Uehara S., Watanabe T., Monden K., Kumon H.
    • Journal Title

      Acta Med Okayama. 63巻

      Pages: 263-272

    • NAID

      120002313204

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of purified newly developed botulinum neurotoxin type A in rat prostate.2009

    • Author(s)
      Nishiyama Y., Yokoyama T., Tomizawa K., Okamura K., Yamamoto Y., Matsui H., Oguma K., Nagai A., Kumon H.
    • Journal Title

      Urology. 74巻

      Pages: 436-439

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Initial Report of Hybrid Radical Prostatectomy for Prostate Cancer : Reduced Bleeding, Clear Vision, and Secure Surgical Margins.2008

    • Author(s)
      Saika T., Kobayashi Y., Watanabe T., Manabe D., Ebara S., Uehara S., Nasu Y., Kumon H.
    • Journal Title

      Acta Med Okayama. 62巻

      Pages: 379-384

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] Cell-penetrating d-isomer peptides of p53 c-terminus : long-term inhibitory effect on the growth of bladder cancer cells.2008

    • Author(s)
      荒木大司
    • Organizer
      103^<rd> Annual Meeting of the American Urological Association.
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2008-05-17
    • Related Report
      2010 Final Research Report
  • [Presentation] 膀胱癌に対する細胞膜透過性ペプチドを用いたD-isomer型p53ペプチド導入治療法の試み2008

    • Author(s)
      荒木大司
    • Organizer
      第96回日本泌尿器科学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-04-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Cell-penetrating d-isomer peptides of p53 c-terminus : long-term inhibitory effect on the growth of bladder cancer cells.2008

    • Author(s)
      荒木大司
    • Organizer
      European Association of Urology 23^<rd> Annual Congress.
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2008-03-26
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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