Melanoma therapy by TRAIL and KATP channel inhibitors
| Project/Area Number |
23591631
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | Nihon University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
OCHIAI Toyoko 日本大学, 医学部, 教授 (40133425)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| 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 / melanoma / KATP / endoplasmic reticulum / ROS |
|---|
| 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.
|
Report
(4 results)
Research Products
(35 results)
