title: Effect of D609 on the expression of GADD45β protein: Potential inhibitory role in the growth of glioblastoma cancer stem like cells.
abstract: 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.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, WI 53792, United States of America. Electronic address: hkalluri@wisc.edu.
authors.forename: Haviryaji S G
authors.initials: HSG
authors.lastname: Kalluri
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, WI 53792, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Kuo
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, WI 53792, United States of America; Cardiovascular Research Center, University of Wisconsin, Madison, WI 53792, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Dempsey
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D009636:Norbornanes; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000255:Adenosine Triphosphate; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D009636:Norbornanes; D012333:RNA, Messenger; D013859:Thiocarbamates; D013871:Thiones; D048051:p38 Mitogen-Activated Protein Kinases; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C046498:tricyclodecane-9-yl-xanthogenate
keywords: GADD45β; Glioma; Survival; Tumor stem cells