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

19 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",

volume = "580",

pages = "4969--4975",

journal = "FEBS Letters",

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number = "20",

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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

KW - Ewing's sarcoma/peripheral primitive neuroectodermal tumor

UR - https://www.scopus.com/pages/publications/33747826981

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DO - 10.1016/j.febslet.2006.07.077

M3 - Article

C2 - 16930595

AN - SCOPUS:33747826981

SN - 0014-5793

VL - 580

SP - 4969

EP - 4975

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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