文章基本信息

标题：A Novel Cyclophane Compound, CPPy, Facilitates NGF-Induced TrkA Signal Transduction and Induces Cell Differentiation in Neuroblastoma
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作者：Yusuke Yamaguchi ; Keiichi Tabata ; Satoru Asami 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：4
页码：638-643
DOI：10.1248/bpb.30.638
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：cyclophane;neuroblastoma;nerve growth factor (NGF);TrkA;differentiation