Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines
Language English Country Greece Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20043138
Knihovny.cz E-resources
- MeSH
- Apoptosis drug effects MeSH
- Cell Differentiation drug effects MeSH
- Cell Cycle drug effects MeSH
- Celecoxib MeSH
- Cyclooxygenase 2 Inhibitors pharmacology MeSH
- Lipoxygenase Inhibitors pharmacology MeSH
- Caffeic Acids pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neuroblastoma drug therapy enzymology pathology MeSH
- Flow Cytometry MeSH
- Pyrazoles pharmacology MeSH
- Sulfonamides pharmacology MeSH
- Tretinoin pharmacology MeSH
- Cell Shape drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- caffeic acid MeSH Browser
- Celecoxib MeSH
- Cyclooxygenase 2 Inhibitors MeSH
- Lipoxygenase Inhibitors MeSH
- Caffeic Acids MeSH
- Pyrazoles MeSH
- Sulfonamides MeSH
- Tretinoin MeSH
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.
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