| Project/Area Number |
25750397
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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 | The Institute of Physical and Chemical Research |
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Principal Investigator |
KAWAMURA Tatsuro 独立行政法人理化学研究所, 長田抗生物質研究室, 基礎科学特別研究員 (60528561)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | がん / Survivin / 活性酸素種 / グルタチオン / KRAS / 細胞死 |
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| Outline of Final Research Achievements |
Using our chemical arrays, we identified NPD926 as a Survivin ligand. We found that NPD926 induced cancer cell death, and elucidated the predominant mechanism of action underlying NPD926-induced cell death: conjugation with and depletion of cellular glutathione, and subsequent generation of reactive oxygen species (ROS), but not Survivin inhibition. NPD926 preferentially induced effects in KRAS-transformed fibroblast cells, compared with their untransformed counterparts. Furthermore, NPD926 sensitized cells to inhibitors of system xc－, a cystine-glutamate antiporter considered as a potential therapeutic target in cancers including cancer stem cells. These data show the effectiveness of a newly identified ROS inducer, which targets glutathione metabolism, in cancer treatment.
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