| Project/Area Number |
15K16563
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Chemical biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Kawamura Tatsuro 国立研究開発法人理化学研究所, 環境資源科学研究センター, 協力研究員 (60528561)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | すい臓がん / 代謝 / 活性酸素種 / MTH1 / 膵臓がん / レドックス |
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| Outline of Final Research Achievements |
Pancreatic cancer is a highly aggressive disease, and development of more effective therapy is desired. In the present study, we identified two compounds which modulate metabolism of pancreatic cancer cells. Compound A inhibits mitochondrial respiration chain complex III, and Compound B inhibits glycolysis.
On the other hand, MTH1 is a hydrolase of oxidized purine nucleoside triphosphates, which attracted attention as a potential cancer therapeutic target. Recently, we identified new MTH1 inhibitors by chemical array screening. Proteomic profiling of small-molecule inhibitors revealed mechanistic differences among chemically distinct MTH1 inhibitors. In addition, overexpression of MTH1 did not rescue cells from MTH1 inhibitor-induced cell death, and siRNA-mediated knockdown of MTH1 did not suppress cancer cell growth. Taken together, we conclude that the cytotoxicity of MTH1 inhibitors is attributable to off-target effects and that MTH1 is not essential for cancer cell survival.
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