| Project/Area Number |
15K09792
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 良弘 日本大学, 医学部, 研究員 (80206549)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 低温大気圧プラズマ / メラノーマ / 腫瘍選択性 / ミトコンドリア / 活性酸素 / 酸化ストレス / アポトーシス / AGP / 抗がん作用 / ミトコンドリアダイナミクス / Drp-1 / TRAIL |
|---|
| Outline of Final Research Achievements |
Plasma-stimulated medium (PSM) has emerged as a cold atmospheric plasma-based anticancer tool because it exhibits cytotoxicity against malignant cells, but not toward normal cells. However, the mechanisms of the anticancer effect and those underlying the tumor-selectivity remain unclear. We found that PSM induced mitochondrial network aberration in human malignant melanoma cells, but not in melanocytes. PSM had reactive oxygen species (ROS), which in turn resulted in the generation of superoxide within the mitochondria. The oxidative stress caused excessive mitochondrial fragmentation, swelling, and clustering, and a caspase-independent cell killing. The heavier mitochondrial network aberration in melanoma cells resulted from their higher sensitivity to mitochondrial ROS accumulation, plasma membrane depolarization, and calcium dysregulation. Our findings indicate the importance of mitochondrial network remodeling as a powerful target for tumor-selective melanoma treatment by PSM.
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