d-609 and Glioblastoma

GADD45β (Growth Arrest and DNA Damage inducible protein) is a stress activated protein which plays an important role in regulating apoptosis, proliferation, DNA repair and potentially may have a role in cancer. In this study we examined the role of anti-oxidative stress on the expression of GADD45β in glioma stem-like cells (GSC). We show that patient derived GSCs have high survival in the absence of exogenous growth factors. Addition of D609 (Tricyclodecan-9-yl-xanthogenate), a known anti-oxidative compound, to GSCs reduced the cellular ATP content with significant effects observed when GSCs were cultured in growth factor free medium. D609 exposure also resulted in a decrease in the protein and an increase in mRNA of GADD45β with a concomitant decline in the survival of cells. However, under similar conditions the phosphorylation of p38 MAP kinase (stress activated MAP kinase), a downstream target of GADD45β, was significantly enhanced in response to D609. Therefore it appears that GADD45β might play a role in glioma stem cell survival and that p38 MAP kinase may not be directly activated by GADD45β. Together these observations suggest that anti-oxidative compounds like D609 can target GADD45β which may be one strategy to curtail the growth of glioma stem like cells.

Topics: Adenosine Triphosphate; Antigens, Differentiation; Antineoplastic Agents; Apoptosis; Bridged-Ring Compounds; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; MAP Kinase Signaling System; Neoplastic Stem Cells; Norbornanes; p38 Mitogen-Activated Protein Kinases; Protein Biosynthesis; RNA, Messenger; Thiocarbamates; Thiones