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Arsenic trioxide concentration determines the fate of Ewing's sarcoma family tumors and neuroblastoma cells in vitro
- Arsenic trioxide concentration determines the fate of Ewing's sarcoma family tumors and neuroblastoma cells in vitro
- Jung H.S.; Kim H.-S.; Lee M.-J.; Shin H.Y.; Ahn H.S.; Ryu K.-H.; Seoh J.-Y.; Kim C.J.; Jang J.J.
- Ewha Authors
- 서주영; 유경하
- SCOPUS Author ID
- 서주영; 유경하
- Issue Date
- Journal Title
- FEBS Letters
- vol. 580, no. 20, pp. 4969 - 4975
- SCI; SCIE; SCOPUS
- Arsenic trioxide (As 2O 3) induces both the differentiation and apoptosis of acute promyelocytic leukemia cells in a concentration dependent manner. We assessed the effects of As 2O 3 in CADO-ES Ewing's sarcoma (ES), JK-GMS peripheral primitive neuroectodermal tumor (PNET), and SH-SY5Y neuroblastoma cells, as they share common histogenetic backgrounds. As 2O 3 at low concentrations (0.1-1 μM) induced SH-SY5Y differentiation, and whereas PNET cells acquired a slightly differentiated phenotype, change was minimal in ES cells. Extracellular signal-regulated kinase 2 (ERK2) was activated at low As 2O 3 concentrations, and PD98059, an inhibitor of MEK-1, blocked SH-SY5Y cell differentiation by As 2O 3. High concentrations (2-10 μM) of As 2O 3 induced the apoptosis in all three cell lines, and this was accompanied by the activation of c-jun N-terminal kinase. The generation of H 2O 2 and activation of caspase 3 were identified as critical components of As 2O 3-induced apoptosis in all of the above cell lines. Fibroblast growth factor 2 enhanced As 2O 3-induced apoptosis in JK-GMS cells. The overall effects of As 2O 3 strongly suggest that it has therapeutic potential for the treatment of ES/PNET. © 2006 Federation of European Biochemical Societies.
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