title: Regulation of neural progenitor cell proliferation by D609: potential role for ERK.
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.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, WI 53792, USA. h.kalluri@neurosurg.wisc.edu
authors.forename: Haviryaji S G
authors.initials: HS
authors.lastname: Kalluri
authors.forename: Anchal
authors.initials: A
authors.lastname: Gusain
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Dempsey
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D058953:Neural Stem Cells / Q000187:drug effects* / Q000201:enzymology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009636:Norbornanes; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*
chemical_list: D001952:Bridged-Ring Compounds; D006131:Growth Inhibitors; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D048049:Extracellular Signal-Regulated MAP Kinases