| Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma cells. | |
| | |
MedLine Citation:
|
PMID: 20799280 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Malignant mesothelioma is an aggressive tumor of serosal surfaces, which is refractory to current treatment options. Arsenic trioxide (As2O3) is used clinically to treat acute promyelocytic leukemia, and also to inhibit proliferation of several solid tumors including hepatoma, esophageal, and gastric cancer in vitro. Here we found that As2O3 inhibited cell viability of a mesothelioma cell line, NCI-H2052. As2O3 induced apoptosis of NCI-H2052 cells, which was accompanied by activation of c-Jun NH2-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, and caspase-3. zVAD-fmk, a broad-spectrum caspase inhibitor, inhibited As2O3-induced apoptosis and activation of caspase-3, but not that of JNK1/2 and ERK1/2. Small interfering RNAs (siRNAs) targeting JNK1/2 suppressed As2O3-induced caspase-3 activation and apoptosis, indicating that JNK1/2 regulate As2O3-induced apoptosis though caspase cascade. Furthermore, JNK1 siRNA abrogated As2O3-induced JNK2 phosphorylation and JNK2 siRNA abrogated As2O3-induced JNK1 phosphorylation, suggesting that JNK1 and JNK2 interact with each other. Moreover, JNK1 siRNA, but not JNK2 siRNA, abrogated As2O3-induced ERK1/2 phosphorylation. JNK2 siRNA together with PD98059, a specific MAPK/ERK kinase inhibitor, suppressed As2O3-induced apoptosis more significantly than JNK2 siRNA alone. These results indicated that As2O3 induces apoptosis of NCI-H2052 cells mainly through JNK1/2 activation, and that ERK1/2 is involved in As2O3-induced apoptosis when JNK1/2 are inactivated. |
| | |
Authors:
|
Ryoji Eguchi; Yoshihiro Fujimori; Hiromi Takeda; Chiharu Tabata; Toshiro Ohta; Kouzo Kuribayashi; Kazuya Fukuoka; Takashi Nakano |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of cellular physiology Volume: 226 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2011 Mar |
Date Detail:
|
Created Date: 2010-12-30 Completed Date: 2011-01-27 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: 762-8 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
|
Department of Thoracic Oncology, Hyogo College of Medicine, Nishinomiya, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Apoptosis
/
drug effects* Arsenicals / pharmacology* Caspases / metabolism Cell Line, Tumor Drug Screening Assays, Antitumor Enzyme Activation / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism* Humans JNK Mitogen-Activated Protein Kinases / metabolism* Mesothelioma / enzymology*, pathology* Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Mitogen-Activated Protein Kinase 8 / metabolism Mitogen-Activated Protein Kinase 9 / metabolism Oxides / pharmacology* |
| Chemical | |
Reg. No./Substance:
|
0/Arsenicals; 0/Oxides; 1327-53-3/arsenic trioxide; EC 2.7.1.24/Mitogen-Activated Protein Kinase 9; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinase 8; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Blood-derived human osteoclast resorption activity is impaired by Hyaluronan-CD44 engagement via a p...
Next Document: Complexity of polycomb group function: Diverse mechanisms of target specificity.