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Overcoming therapy resistance of glioma cells via modulation of mitochondrial energy metabolism

Research Project

Project/Area Number 20791002
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionYamagata University

Principal Investigator

TOMIYAMA Arata  Yamagata University, 医学部, 助教 (40385810)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsグリオーマ / エネルギー代謝
Research Abstract

Cancer cells are prone to carry out anaerobic glycolysis even in the presence of ample oxygen. This unique property of cancer cells is widely known as "Warburg effect", but why cancer cells choose to carry out such an energetically-inefficient, anaerobic metabolism in the place of oxidative metabolism, which is far more efficient in terms of ATP production, has remained a big enigma for decades in the field of cancer research. As a possible explanation, we have recently shown that oxidative phosphorylation, but not anaerobic glycolysis, is required for the activation of Bax and Bak, an essential step in the process of mitochondria-mediated apoptosis. Thus, Warburg effect could be a crafty strategy of cancer cells to evade apoptosis at the expense of energy production efficiency. Conversely, our findings also suggested the possibility that reversal of Warburg effect could render cancer cells susceptible to mitochondria-mediated apoptosis and hence to anti-cancer therapies. In this project, therefore, we searched for natural and chemical compounds that recover/promote oxidative metabolism in glioma cells and thereby render the cells sensitive to temozolomide, the first-choice chemotherapeutic agent in the management of malignant gliomas. Here we report that we have successfully identified a natural compound having such activities.

Report

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

    (12 results)

All 2010 2009 2008

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (8 results)

  • [Journal Article] Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR.2010

    • Author(s)
      Sato A, Sunayama J, Matsuda K, Tachibana K, Sakurada K, Tomiyama A, Kayama T, Kitanaka C.
    • Journal Title

      Neurosci Lett 470

      Pages: 115-120

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR2010

    • Author(s)
      Sato A, et al.
    • Journal Title

      Neurosci Lett 470

      Pages: 115-120

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of Ras C-terminal processing by JNK inhibition.2008

    • Author(s)
      Mouri W, Tachibana K, Tomiyama A, Sunayama J, Sato A, Sakurada K, Kayama T, Kitanaka C.
    • Journal Title

      Biochem Biophys Res Commun 371

      Pages: 273-277

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of Ras C-terminal processing by JNK inhibition2008

    • Author(s)
      Mouri W
    • Journal Title

      Biochem Biophys Res Commun 371

      Pages: 273-277

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Effect of rapamycin (mTOR inhibitor) and LY294002 (PI3K inhibitor) on glioblastoma stem-like cells.2009

    • Author(s)
      Sunayama J, Sato A, Matsuda K, Tachibana K, Tomiyama A, Sakurada K, Kayama T, Kitanaka C
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Final Research Report
  • [Presentation] Mechanism of heavy ion radiation-induced glioma cell death.2009

    • Author(s)
      Tomiyama A, Sunayama J, Tachibana K, Matsuda K, Ando K, Kayama T, Kitanaka C
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Final Research Report
  • [Presentation] Mechanism of heavy ion radiation-induced glioma cell death2009

    • Author(s)
      Tomiyama A, et al.
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒトグリオーマ細胞株A172における腫瘍幹細胞の単離・同定の試み.2008

    • Author(s)
      佐藤篤, 砂山潤, 松田憲一朗, 立花研, 富山新太, 櫻田香, 北中千史, 嘉山孝正
    • Organizer
      第26回日本脳腫瘍学会
    • Place of Presentation
      松山
    • Year and Date
      2008-11-30
    • Related Report
      2009 Final Research Report
  • [Presentation] ヒトグリオーマ細胞株A172における腫瘍幹細胞の単離同定の試み2008

    • Author(s)
      佐藤篤
    • Organizer
      第26回日本脳腫瘍学会
    • Place of Presentation
      松山
    • Year and Date
      2008-11-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mechanism of heavy ion radiation-induced cancer cell death.2008

    • Author(s)
      Tomiyama A, Nomiya T, Kitanaka C, Nemoto K, Yamashita H, Ando K, Kayama T
    • Organizer
      HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉
    • Year and Date
      2008-04-15
    • Related Report
      2009 Final Research Report
  • [Presentation] Isolation and characterization of cancer stem-like cells from a human glioblastoma cell line A172.2008

    • Author(s)
      Sato A, Sunayama J, Sakurada K, Matsuda K, Tachibana K, Tomiyama A, Kitanaka C, Kayama T
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2009 Final Research Report
  • [Presentation] Downregulation of Ras C-terminal Processing by JNK Inhibition.2008

    • Author(s)
      Mouri W, Tachibana K, Tomiyama A, Sunayama J, Sato A, Sakurada K, Kayama T, Kitanaka C
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2009 Final Research Report

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

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