Arsenic trioxide concentration determines the fate of Ewing's sarcoma family tumors and neuroblastoma cells in vitro

Hyun Sook Jung, Han Seong Kim, Min Jae Lee, Hee Young Shin, Hyo Seop Ahn, Kyung Ha Ryu, Ju Young Seoh, Chong Jai Kim, Ja June Jang

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18 Scopus citations


Arsenic trioxide (As2O3) induces both the differentiation and apoptosis of acute promyelocytic leukemia cells in a concentration dependent manner. We assessed the effects of As2O3 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. As2O3 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 As2O3 concentrations, and PD98059, an inhibitor of MEK-1, blocked SH-SY5Y cell differentiation by As2O3. High concentrations (2-10 μM) of As2O3 induced the apoptosis in all three cell lines, and this was accompanied by the activation of c-jun N-terminal kinase. The generation of H2O2 and activation of caspase 3 were identified as critical components of As2O3-induced apoptosis in all of the above cell lines. Fibroblast growth factor 2 enhanced As2O3-induced apoptosis in JK-GMS cells. The overall effects of As2O3 strongly suggest that it has therapeutic potential for the treatment of ES/PNET.

Original languageEnglish
Pages (from-to)4969-4975
Number of pages7
JournalFEBS Letters
Issue number20
StatePublished - 4 Sep 2006

Bibliographical note

Funding Information:
This work was supported in part by Grant No. R01-2001-000-00128-0 from the Korea Science & Engineering Foundation and in part by the BK21 Program for Medicine, Dentistry and Pharmacy, 2003.


  • Arsenic trioxide
  • Ewing's sarcoma/peripheral primitive neuroectodermal tumor


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