| Project/Area Number |
25861056
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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 |
Radiation science
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| Research Institution | Hirosaki University |
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Principal Investigator |
SATO Mariko 弘前大学, 医学部附属病院, その他 (30645263)
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 低酸素 / HIF-1阻害剤 / アポトーシス / ミトコンドリア脱分極 / 活性酸素 / LW6 / 上皮間葉転換 / JNK / HIF-1a阻害剤 |
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| Outline of Final Research Achievements |
Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that act on the adaptation of cancer cells to hypoxia. LW6, a recently developed HIF-1 inhibitor, is expected to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF-1α.
In this study, we revealed that LW6 induced hypoxia-selective apoptosis together with the loss of mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6-treated hypoxic A549 cells and LW6 induced a hypoxia-selective increase of mitochondrial reactive oxygen species.
In conclusion, LW6 inhibits the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain has emerged as a useful strategy to maneuver apoptosis in cancer cells.
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