Compounds > 2-2-bis(hydroxymethyl)-1-azabicyclo(2-2-2-)octan-3-one

2-2-bis(hydroxymethyl)-1-azabicyclo(2-2-2-)octan-3-one and Glioma

2-2-bis(hydroxymethyl)-1-azabicyclo(2-2-2-)octan-3-one has been researched along with Glioma* in 1 studies

Other Studies

1 other study(ies) available for 2-2-bis(hydroxymethyl)-1-azabicyclo(2-2-2-)octan-3-one and Glioma

Article	Year
A novel p53 rescue compound induces p53-dependent growth arrest and sensitises glioma cells to Apo2L/TRAIL-induced apoptosis. Cell death and differentiation, 2008, Volume: 15, Issue:4 Reactivation of mutant p53 in tumours is a promising strategy for cancer therapy. Here we characterise the novel p53 rescue compound P53R3 that restores sequence-specific DNA binding of the endogenously expressed p53(R175H) and p53(R273H) mutants in gel-shift assays. Overexpression of the paradigmatic p53 mutants p53(R175H), p53(R248W) and p53(R273H) in the p53 null glioma cell line LN-308 reveals that P53R3 induces p53-dependent antiproliferative effects with much higher specificity and over a wider range of concentrations than the previously described p53 rescue drug p53 reactivation and induction of massive apoptosis (PRIMA-1). Furthermore, P53R3 enhances recruitment of endogenous p53 to several target promoters in glioma cells bearing mutant (T98G) and wild-type (LNT-229) p53 and induces mRNA expression of numerous p53 target genes in a p53-dependent manner. Interestingly, P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5) whereas CD95 and TNF receptor 1 levels are unaffected. Accordingly, P53R3 does not sensitise for CD95 ligand- or tumour necrosis factor alpha-induced cell death, but displays synergy with Apo2L.0 in 9 of 12 glioma cell lines. Both DR5 surface induction and synergy with Apo2L.0 are sensitive to siRNA-mediated downregulation of p53. Thus this new p53 rescue compound may open up novel perspectives for the treatment of cancers currently considered resistant to the therapeutic induction of apoptosis. Topics: Animals; Antineoplastic Agents; Apoptosis; Aza Compounds; Brain Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Gene Expression Regulation, Neoplastic; Glioma; Humans; Mutation; Promoter Regions, Genetic; Quinazolines; Rats; Rats, Sprague-Dawley; Receptors, TNF-Related Apoptosis-Inducing Ligand; RNA Interference; RNA, Messenger; RNA, Small Interfering; TNF-Related Apoptosis-Inducing Ligand; Transfection; Tumor Suppressor Protein p53; Up-Regulation; Valine	2008

Article

Year

A novel p53 rescue compound induces p53-dependent growth arrest and sensitises glioma cells to Apo2L/TRAIL-induced apoptosis.

Cell death and differentiation, 2008, Volume: 15, Issue:4

Reactivation of mutant p53 in tumours is a promising strategy for cancer therapy. Here we characterise the novel p53 rescue compound P53R3 that restores sequence-specific DNA binding of the endogenously expressed p53(R175H) and p53(R273H) mutants in gel-shift assays. Overexpression of the paradigmatic p53 mutants p53(R175H), p53(R248W) and p53(R273H) in the p53 null glioma cell line LN-308 reveals that P53R3 induces p53-dependent antiproliferative effects with much higher specificity and over a wider range of concentrations than the previously described p53 rescue drug p53 reactivation and induction of massive apoptosis (PRIMA-1). Furthermore, P53R3 enhances recruitment of endogenous p53 to several target promoters in glioma cells bearing mutant (T98G) and wild-type (LNT-229) p53 and induces mRNA expression of numerous p53 target genes in a p53-dependent manner. Interestingly, P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5) whereas CD95 and TNF receptor 1 levels are unaffected. Accordingly, P53R3 does not sensitise for CD95 ligand- or tumour necrosis factor alpha-induced cell death, but displays synergy with Apo2L.0 in 9 of 12 glioma cell lines. Both DR5 surface induction and synergy with Apo2L.0 are sensitive to siRNA-mediated downregulation of p53. Thus this new p53 rescue compound may open up novel perspectives for the treatment of cancers currently considered resistant to the therapeutic induction of apoptosis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Aza Compounds; Brain Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Gene Expression Regulation, Neoplastic; Glioma; Humans; Mutation; Promoter Regions, Genetic; Quinazolines; Rats; Rats, Sprague-Dawley; Receptors, TNF-Related Apoptosis-Inducing Ligand; RNA Interference; RNA, Messenger; RNA, Small Interfering; TNF-Related Apoptosis-Inducing Ligand; Transfection; Tumor Suppressor Protein p53; Up-Regulation; Valine

2008