2014 Fiscal Year Final Research Report
Identification of novel candidate chemical compounds targeting TrkB to induce apoptosis in neuroblastoma
| Project/Area Number |
24592703
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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 |
Pediatric surgery
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| Research Institution | Chiba Cancer Center (Research Institute) |
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Principal Investigator |
NAKAMURA Yohko 千葉県がんセンター(研究所), がん予防センター, 主席研究員 (60260254)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWARA Akira (50117181)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 神経芽腫 / TrkB / 低分子化合物 / BDNF / 細胞死 |
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| Outline of Final Research Achievements |
The neurotrophin receptor TrkB and its ligand BDNF are expressed at high levels in high-risk NBs and are involved in defining the poor prognosis of the patients. We performed an in silico screening procedure utilizing an AutoDock/grid computing technology in order to identify novel small chemical compounds targeting the BDNF binding domain of TrkB. We have finally identified seven compounds that kill NB cells. The TUNEL assay showed that these molecules induce apoptosis accompanied by p53 activation in NB cell lines. The candidate compounds and BDNF demonstrated an antagonistic effect on cell growth, invasion and colony formation, possibly suggesting competition at the BDNF binding site of TrkB. The candidate compounds had tumor suppressive activity in xenograft and in vivo toxicity tests using mice. Using in silico Docking screening we have found new candidate TrkB inhibitors against high-risk NBs, which could lead to new anti-cancer drugs.
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| Free Research Field |
分子生物学
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