2013 Fiscal Year Final Research Report
Melanoma therapy by TRAIL and KATP channel inhibitors
| Project/Area Number |
23591631
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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) |
2011 – 2013
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| Keywords | TRAIL / ATP感受性カリウムチャネル / メラノーマ / アポトーシス / ミトコンドリア / 活性酸素 |
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| Research Abstract |
The major findings of this research project are that:(1) the potentiation of the apoptosis by KATP channel inhibitors is a general phenomenon among cancer cells with different origins, including leukemia and lung cancer cells; (2) the effects of these channel inhibitors including depolarization induction are tumor-selective; (3) the potentiation of apoptosis occurs through upregulation of TRAIL receptors-1/2 and increased mitochondrial and endoplasmic reticulum death pathways; (4) mitochondrial reactive oxygen species (ROS) mediate the activation of death signaling pathways, and depolarization and ROS mutually regulate one another. The findings provide a molecular basis of the combined use of TRAIL and KATP channel inhibitors in the treatment of TRAIL-resistant cancer cells in connection with the emerging concept that oxidative stress is a critical mediator of mitochondrial and endoplasmic reticulum dysfunctions and serves as a tumor-selective target in cancer treatment.
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Research Products
(13 results)
