Document Detail


MK886-induced apoptosis depends on the 5-LO expression level in human malignant glioma cells.
MedLine Citation:
PMID:  19862483     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mounting evidence suggests that lipoxygenase (LO)-catalyzed products may play a key role in the development and progression of human cancers. In this study, we analyzed the effects of a 5-LO inhibitor, which inhibits the conversion of arachidonic acid to leukotrienes, on cell proliferation and apoptosis in human malignant glioma cells, including 5-LO-expressing cells U-87MG, A172 and 5-LO non-expressing cell U373. Growth of U-87MG and A172 cells, but not that of U373 cells, was inhibited in a dose-dependent manner by treatment with MK886. Similarly, specific 5-LO silencing by small interfering RNA reduced the growth of U-87MG and A172 cells. MK886 treatment reduced 5-LO activity independently of 5-LO-activating protein (FLAP) in human malignant glioma cells. MK886 treatment also induced cell apoptosis, measured by DNA fragmentation and nuclear condensation, in U-87MG and A172 cells but there were no signs in U373 cells. Moreover, this treatment reduced ERKs phosphorylation and anti-apoptotic molecule Bcl-2 expression, and increased Bax expression in U-87MG and A172 cells. In summary, our results show there is a link between the 5-LO expression status and the extent of MK886-inhibited cell proliferation and apoptosis. Taken together, this study suggest that 5-LO is a possible target for treating patients with gliomas, and 5-LO inhibition might be potent therapy for patients with 5-LO-expressing malignant gliomas.
Authors:
Jung Yeon Lim; Ji Hyeon Oh; Ju Ri Jung; Seong Muk Kim; Chung Hun Ryu; Hong-Tae Kim; Sin-Soo Jeun
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-28
Journal Detail:
Title:  Journal of neuro-oncology     Volume:  97     ISSN:  1573-7373     ISO Abbreviation:  J. Neurooncol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-07-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309335     Medline TA:  J Neurooncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  339-46     Citation Subset:  IM    
Affiliation:
Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / genetics,  metabolism
Arachidonate 5-Lipoxygenase / genetics,  metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Flow Cytometry / methods
Gene Expression Regulation, Neoplastic / drug effects*
Glioma / pathology*
Humans
Indoles / pharmacology*
Lipoxygenase Inhibitors / pharmacology*
Mutation / genetics
RNA, Small Interfering / genetics,  pharmacology
Time Factors
Transfection / methods
Tumor Suppressor Protein p53 / genetics
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Indoles; 0/Lipoxygenase Inhibitors; 0/RNA, Small Interfering; 0/Tumor Suppressor Protein p53; 118414-82-7/L 663536; EC 1.13.11.34/Arachidonate 5-Lipoxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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