Regulation of neural progenitor cell proliferation by D609: potential role for ERK

Mol Neurobiol. 2013 Apr;47(2):782-9. doi: 10.1007/s12035-012-8390-6. Epub 2012 Dec 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged-Ring Compounds / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • 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*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / enzymology*
  • Norbornanes
  • Phosphorylation / drug effects
  • Rats
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / enzymology*
  • Thiocarbamates
  • Thiones / pharmacology*

Substances

  • Bridged-Ring Compounds
  • Growth Inhibitors
  • Norbornanes
  • Thiocarbamates
  • Thiones
  • tricyclodecane-9-yl-xanthogenate
  • Extracellular Signal-Regulated MAP Kinases