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

doi:10.1016/j.febslet.2006.07.077

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

Department of Pediatrics

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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 language	English
Pages (from-to)	4969-4975
Number of pages	7
Journal	FEBS Letters
Volume	580
Issue number	20
DOIs	https://doi.org/10.1016/j.febslet.2006.07.077
State	Published - 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.

Keywords

Arsenic trioxide
Ewing's sarcoma/peripheral primitive neuroectodermal tumor

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10.1016/j.febslet.2006.07.077

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@article{910cf51a1e2d473382ebf053188cd382,

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

abstract = "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.",

keywords = "Arsenic trioxide, Ewing's sarcoma/peripheral primitive neuroectodermal tumor",

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

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.",

year = "2006",

month = sep,

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doi = "10.1016/j.febslet.2006.07.077",

language = "English",

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journal = "FEBS Letters",

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T1 - Arsenic trioxide concentration determines the fate of Ewing's sarcoma family tumors and neuroblastoma cells in vitro

AU - Jung, Hyun Sook

AU - Kim, Han Seong

AU - Lee, Min Jae

AU - Shin, Hee Young

AU - Ahn, Hyo Seop

AU - Ryu, Kyung Ha

AU - Seoh, Ju Young

AU - Kim, Chong Jai

AU - Jang, Ja June

N1 - 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.

PY - 2006/9/4

Y1 - 2006/9/4

N2 - 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.

AB - 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.

KW - Arsenic trioxide

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DO - 10.1016/j.febslet.2006.07.077

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SN - 0014-5793

VL - 580

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JO - FEBS Letters

JF - FEBS Letters

IS - 20

ER -

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

Abstract

Bibliographical note

Keywords

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