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Updated: Jun 13, 2026
Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
Published on: April 12, 2015
Enhancement of ATRA-induced differentiation of neuroblastoma cells with LOX/COX inhibitors: an expression profiling
Petr Chlapek1, Martina Redova, Karel Zitterbart
1Laboratory of Tumor Biology and Genetics, Department of Experimental Biology, School of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic.
Background:
We performed expression profiling of two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, after combined treatment with all-trans retinoic acid (ATRA) and inhibitors of lipoxygenases (LOX) and cyclooxygenases (COX). This study is a continuation of our previous work confirming the possibility of enhancing ATRA-induced cell differentiation in these cell lines by the application of LOX/COX inhibitors and brings more detailed information concerning the mechanisms of the enhancement of ATRA-induced differentiation of neuroblastoma cells.
Methods:
Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor on cyclooxygenase-2, were used in this study. Expression profiling was performed using Human Cancer Oligo GEArray membranes that cover 440 cancer-related genes.
Results:
Cluster analyses of the changes in gene expression showed the concentration-dependent increase in genes known to be involved in the process of retinoid-induced neuronal differentiation, especially in cytoskeleton remodeling. These changes were detected in both cell lines, and they were independent of the type of specific inhibitors, suggesting a common mechanism of ATRA-induced differentiation enhancement. Furthermore, we also found overexpression of some genes in the same cell line (SK-N-BE(2) or SH-SY5Y) after combined treatment with both ATRA and CA, or ATRA and CX. Finally, we also detected that gene expression was changed after treatment with the same inhibitor (CA or CX) in combination with ATRA in both cell lines.
Conclusions:
Obtained results confirmed our initial hypothesis of the common mechanism of enhancement in ATRA-induced cell differentiation via inhibition of arachidonic acid metabolic pathway.
Insights
Combining all-trans retinoic acid (ATRA) with lipoxygenase (LOX) or cyclooxygenase (COX) inhibitors enhances neuroblastoma cell differentiation. This suggests a common mechanism involving the arachidonic acid pathway for improved retinoid therapy.
Area of Science:
- Neuroscience
- Molecular Biology
- Cancer Research
Background:
- Neuroblastoma cell differentiation can be enhanced by all-trans retinoic acid (ATRA) combined with lipoxygenase (LOX) and cyclooxygenase (COX) inhibitors.
- This study investigates the underlying mechanisms of this enhancement in SK-N-BE(2) and SH-SY5Y neuroblastoma cell lines.
Purpose of the Study:
- To elucidate the molecular mechanisms by which LOX/COX inhibitors enhance ATRA-induced differentiation in neuroblastoma cells.
- To identify specific gene expression changes associated with this combined treatment.
Main Methods:
- Gene expression profiling using Human Cancer Oligo GEArray membranes (440 cancer-related genes).
- Treatment of neuroblastoma cell lines (SK-N-BE(2), SH-SY5Y) with ATRA in combination with caffeic acid (5-LOX inhibitor) or celecoxib (COX-2 inhibitor).
Main Results:
- Cluster analysis revealed a concentration-dependent increase in genes related to neuronal differentiation and cytoskeleton remodeling.
- Gene expression changes were consistent across both cell lines and independent of the specific LOX/COX inhibitor used, indicating a common enhancement mechanism.
- Overexpression of specific genes was observed following combined ATRA and inhibitor treatments.
Conclusions:
- The findings confirm a shared mechanism for enhancing ATRA-induced differentiation through the inhibition of the arachidonic acid metabolic pathway.
- This provides a deeper understanding of retinoid therapy for neuroblastoma and potential therapeutic strategies.
