The enhancement of radiation and hyperthermia induced, mitochondria targeted cell death

• Project/Area Number: 24591835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: University of Toyama
• Principal Investigator: ZHAO Qing-Li 富山大学, 大学院医学薬学研究部(医学), 助教 (90313593)
• Research Collaborator: FUJIWARA Yoshisada 富山大学, 大学院医学薬学研究部(医), 協力研究員(神戸大学名誉教授) ; KONDO Takashi 富山大学, 大学院医学薬学研究部(医), 教授
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 細胞死 / 温熱 / 放射線 / 放射線治療生物学

Outline of Final Research Achievements

In this study, we identified that Tempo combine treatment with hyperthermia rapidly induced autophagic cell death in U937 and HeLa cells. This co-treatment inhibited the processing of heat-activated procaspase-3 into active small subunits, leading to the inhibition of caspase-dependent apoptosis, and instead caused the induction of autophagy. The inactivation of caspases, a key event, could result from oxidation of active-site-CysSH of all caspases by a prooxidant oxo-ammonium cation, an intermediate derived Tempo during dismutation of hyperthermia-induced superoxide anion. In addition, the co-treatment caused mitochondrial dysfunction, and liberation of Beclin 1 from the Bcl-2/Beclin 1 complex, all of which contributed to induction of autophagy. These autophagic cells are leading to the complete proliferative inhibition. Thus, Tempo is a unique thermosensitizer to synergistically induce apoptosis and autophagic cell death.

Research Products

• [Presentation] Tempo combination treatment with hyperthermia switch the cell death from apoptosis to autophagy (2014)
  • Author(s): Zhao Qing-Li, Fujiwara Yoshisada, Kondo Takashi
  • Organizer: BIT's 7th Annual World Cancer Congress-2014
  • Place of Presentation: Jinling convention center, Nanjing, China
  • Year and Date: 2014-05-16 – 2014-05-18
• [Presentation] Tempo enhanced radiation- or heat-induced cell death (2013)
  • Author(s): 趙 慶利、藤原美定、近藤 隆
  • Organizer: The 3rd Asian Congress of Radiation Research
  • Place of Presentation: Bejing, China