Regulation of Neural Progenitor Cell Proliferation by D609: Potential Role for ERK

Tricyclodecan-9-yl-xanthogenate (D609) has been shown to possess both neuroprotective and anti-proliferative properties. We investigated the role of D609 in reducing the proliferation of neural progenitor cells in vitro. D609 decreased the expression of cyclin D1 after 1 day but not 2 or 4 days in c...

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Bibliographic Details
Published in:Molecular neurobiology 2013-04, Vol.47 (2), p.782-789
Main Authors: Kalluri, Haviryaji S. G., Gusain, Anchal, Dempsey, Robert J.
Format: Article
Language:English
Subjects:
AKT protein
Animals
Biomedical and Life Sciences
Biomedicine
Bridged-Ring Compounds - pharmacology
Cell Biology
Cell cycle
Cell Proliferation - drug effects
Cells, Cultured
Cyclin-dependent kinases
Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases - physiology
Growth Inhibitors - pharmacology
Humans
Neural Stem Cells - drug effects
Neural Stem Cells - enzymology
Neurobiology
Neurology
Neurons - cytology
Neurons - drug effects
Neurons - enzymology
Neurosciences
Phosphorylation
Phosphorylation - drug effects
Rats
Signal transduction
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - enzymology
Thiones - pharmacology
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Summary:Tricyclodecan-9-yl-xanthogenate (D609) has been shown to possess both neuroprotective and anti-proliferative properties. We investigated the role of D609 in reducing the proliferation of neural progenitor cells in vitro. D609 decreased the expression of cyclin D1 after 1 day but not 2 or 4 days in culture, indicating the possible degradation/inactivation of drug in the medium. Consistent with this notion, spectral analysis showed the maximum absorbance of D609 (100 μM) at 300 nm, which decreased by ~30 % following incubation at 37 °C for 24 h. Further experiments revealed that incubation of neural progenitor cells with D609 decreased the phosphorylation of extracellular signal-regulated kinase (ERK) but not Akt. In addition, increasing the concentration of B27 (1–4 %), but not FGF2, diminished the effect of D609 on cell proliferation. These results together suggest that D609 may curtail the proliferation of neural progenitor cells by decreasing the ERK-mediated expression of cyclin D1 and may have a therapeutic potential in containing the proliferation of tumor stem cells.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-012-8390-6