| Project/Area Number |
15K09750
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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(Renkei-kenkyūsha) |
OCHIAI Toyoko 日本大学, 医学部, 教授 (40133425)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | TRAIL / 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 / カルシウム / 細胞膜脱分極 / ROS / アポト－シス / がん / 抗がん作用 / ミトコンドリアダイナミクス / アポトーシス |
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| Outline of Final Research Achievements |
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a next-generation anticancer drug owing to it tumor-specific cytotoxicity. However, the mechanisms underlying the tumor-selective cell killing remain mostly unclear. We found that TRAIL evoked mitochondrial network aberration in human malignant melanoma cells, but not in non-transformed cells. Excessive fragmentation, swelling, and clustering of the mitochondria played critical roles in triggering cell killing. Hydrogen peroxide and superoxide within the mitochondria participated in the pro-death mitochondrial network aberration, and melanoma cells were more susceptible than melanocytes to the oxidative stress. Moreover, we found that plasma membrane depolarization and calcium dysregulation promoted the mitochondrial network aberration and TRAIL effectiveness. Our findings indicate that TRAIL elicits its tumor-selective anticancer activity by targeting the mitochondrial network remodeling.
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