Document Detail

Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines.
MedLine Citation:
PMID:  20043138     Owner:  NLM     Status:  MEDLINE    
We investigated the possible modulation by LOX/ COX inhibitors of all-trans retinoic acid (ATRA)-induced cell differentiation in two established neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor of cyclooxygenase-2, were chosen for this study. The effects of the combined treatment with ATRA and LOX/COX inhibitors on neuroblastoma cells were studied using cell morphology assessment, detection of differentiation markers by immunoblotting, measurement of proliferation activity, and cell cycle analysis and apoptosis detection by flow cytometry. The results clearly demonstrated the potential of caffeic acid to enhance ATRA-induced cell differentiation, especially in the SK-N-BE(2) cell line, whereas application of celecoxib alone or with ATRA led predominantly to cytotoxic effects in both cell lines. Moreover, the higher sensitivity of the SK-N-BE(2) cell line to combined treatment with ATRA and LOX/COX inhibitors suggests that cancer stem cells are a main target for this therapeutic approach. Nevertheless, further detailed study of the phenomenon of enhanced cell differentiation by expression profiling is needed.
Martina Redova; Petr Chlapek; Tomas Loja; Karel Zitterbart; Marketa Hermanova; Jaroslav Sterba; Renata Veselska
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  25     ISSN:  1791-244X     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2009-12-31     Completed Date:  2010-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  271-80     Citation Subset:  IM    
Laboratory of Tumor Biology and Genetics, Institute of Experimental Biology, School of Science, Masaryk University, 61137 Brno, Czech Republic.
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MeSH Terms
Apoptosis / drug effects
Caffeic Acids / pharmacology
Cell Cycle / drug effects
Cell Differentiation / drug effects
Cell Line, Tumor
Cell Shape / drug effects
Cyclooxygenase 2 Inhibitors / pharmacology*
Flow Cytometry
Lipoxygenase Inhibitors / pharmacology*
Neuroblastoma / drug therapy*,  enzymology,  pathology
Pyrazoles / pharmacology
Sulfonamides / pharmacology
Tretinoin / pharmacology*
Reg. No./Substance:
0/Caffeic Acids; 0/Cyclooxygenase 2 Inhibitors; 0/Lipoxygenase Inhibitors; 0/Pyrazoles; 0/Sulfonamides; 169590-42-5/celecoxib; 302-79-4/Tretinoin; 331-39-5/caffeic acid

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