A Novel Cyclophane Compound, CPPy, Facilitates NGF-Induced TrkA Signal Transduction and Induces Cell Differentiation in Neuroblastoma
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- Yamaguchi Yusuke
- Clinical Pharmacy, College of Pharmacy, Nihon University
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- Tabata Keiichi
- Clinical Pharmacy, College of Pharmacy, Nihon University
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- Asami Satoru
- Clinical Pharmacy, College of Pharmacy, Nihon University
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- Miyake Muneharu
- Medicinal Chemistry, College of Pharmacy, Nihon University
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- Suzuki Takashi
- Clinical Pharmacy, College of Pharmacy, Nihon University Department of Pediatrics, School of Medicine, Nihon University
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Neuroblastoma (NB) often causes spontaneously regression, and can mature to ganglioneuroma. The form with the most favorable prognosis expresses high levels of TrkA, a high-affinity receptor for nerve growth factor (NGF), whereas advanced NB and associated cell lines have abnormalities in the NGF/TrkA signaling pathway. A novel cyclophane, cyclophane pyridine (CPPy), was designed to conserve the tyrosine phosphorylation of TrkA, thereby enhancing NGF/TrkA signal transduction. We investigated whether this compound improved NGF-induced tyrosine phosphorylation of the Y490 domain of TrkA and conserved the expression of an early gene (c-fos) in human NB cell lines (IMR-32 and NB-39). As determined by Western blotting, TrkA (Y490) phosphorylation was enhanced by the combination of CPPy (10−8 M) and NGF (100 ng/ml) compared with NGF alone. CPPy also conserved NGF-induced c-fos mRNA expression. Moreover, CPPy induced the morphological differentiation of NB cells, leading to expression of the neuronal marker gene GAP-43. These data suggest that CPPy can induce the differentiation of NB cell lines by facilitating NGF-induced TrkA/Ras/MAPK signal transduction, and may therefore be an effective therapeutic agent for NB.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 30 (4), 638-643, 2007
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679602657280
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- NII論文ID
- 110006271197
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD2sXls1akt7g%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 8690817
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- PubMed
- 17409494
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
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- 使用不可