cytochrome-c-t and 2-2-bis(hydroxymethyl)-1-azabicyclo(2-2-2-)octan-3-one

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

Other Studies

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

Article	Year
PRIMA-1MET induces mitochondrial apoptosis through activation of caspase-2. Oncogene, 2008, Nov-20, Volume: 27, Issue:51 p53 mutations occur frequently in human tumors. The low-molecular-weight compound PRIMA-1(MET) reactivates mutant p53, induces apoptosis in human tumor cells and inhibits tumor xenograft growth in vivo. Here, we show that PRIMA-1(MET) induces mutant p53-dependent mitochondria-mediated apoptosis through activation of caspase-2 with subsequent cytochrome c release and further activation of downstream caspase-9 and caspase-3. Inhibition of caspase-2 by a selective inhibitor and/or siRNA prevents cytochrome c release on PRIMA-1(MET) treatment and causes a significant reduction in PRIMA-1(MET)-induced cell death. Our findings highlight a chain of cellular events triggered by PRIMA-1(MET) that lead to apoptotic cell death. This should facilitate further development and optimization of efficient PRIMA-1(MET)-based anticancer drugs. Topics: Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Apoptosis; Aza Compounds; Bridged Bicyclo Compounds, Heterocyclic; Caspase 2; Caspase 3; Caspase 9; Caspase Inhibitors; Cytochromes c; Drug Evaluation, Preclinical; Enzyme Activation; Enzyme Inhibitors; Genes, p53; Humans; Membrane Potential, Mitochondrial; Mitochondria; Quinuclidines; Tissue Distribution; Tumor Cells, Cultured	2008
Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer cell, 2003, Volume: 4, Issue:5 Recent efforts to develop pharmacologic agents that restore function to mutant forms of p53 hold significant promise in cancer therapy. Here, we examine the effects of such pharmacologic activation of p53 function using a small molecule, PRIMA-1, and a model system employing a p53 protein fused to a mutant steroid binding domain of the murine estrogen receptor (p53ERtam) that renders it responsive only in the presence of 4-hydroxytamoxifen. In either case, p53 activation triggered apoptosis that was not inhibited by the presence of macromolecular synthesis inhibitors. This p53-induced, transcription-independent apoptosis is Bax dependent, proceeds in the absence of a nucleus, and involves Bax translocation and cytochrome c release. Hence, pharmacologic p53 modulators can activate a transcription-independent apoptotic program. Topics: Animals; Apoptosis; Aza Compounds; bcl-2-Associated X Protein; Bridged Bicyclo Compounds, Heterocyclic; Cell Nucleus; Cells, Cultured; Cloning, Molecular; Cytochromes c; Fibroblasts; Humans; Mice; Mitochondria; Mutation; Protein Synthesis Inhibitors; Protein Transport; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Recombinant Fusion Proteins; Tamoxifen; Transcription, Genetic; Tumor Cells, Cultured; Tumor Suppressor Protein p53	2003

Article

Year

PRIMA-1MET induces mitochondrial apoptosis through activation of caspase-2.

Oncogene, 2008, Nov-20, Volume: 27, Issue:51

p53 mutations occur frequently in human tumors. The low-molecular-weight compound PRIMA-1(MET) reactivates mutant p53, induces apoptosis in human tumor cells and inhibits tumor xenograft growth in vivo. Here, we show that PRIMA-1(MET) induces mutant p53-dependent mitochondria-mediated apoptosis through activation of caspase-2 with subsequent cytochrome c release and further activation of downstream caspase-9 and caspase-3. Inhibition of caspase-2 by a selective inhibitor and/or siRNA prevents cytochrome c release on PRIMA-1(MET) treatment and causes a significant reduction in PRIMA-1(MET)-induced cell death. Our findings highlight a chain of cellular events triggered by PRIMA-1(MET) that lead to apoptotic cell death. This should facilitate further development and optimization of efficient PRIMA-1(MET)-based anticancer drugs.

Topics: Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Apoptosis; Aza Compounds; Bridged Bicyclo Compounds, Heterocyclic; Caspase 2; Caspase 3; Caspase 9; Caspase Inhibitors; Cytochromes c; Drug Evaluation, Preclinical; Enzyme Activation; Enzyme Inhibitors; Genes, p53; Humans; Membrane Potential, Mitochondrial; Mitochondria; Quinuclidines; Tissue Distribution; Tumor Cells, Cultured

2008

Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription.

Cancer cell, 2003, Volume: 4, Issue:5

Recent efforts to develop pharmacologic agents that restore function to mutant forms of p53 hold significant promise in cancer therapy. Here, we examine the effects of such pharmacologic activation of p53 function using a small molecule, PRIMA-1, and a model system employing a p53 protein fused to a mutant steroid binding domain of the murine estrogen receptor (p53ERtam) that renders it responsive only in the presence of 4-hydroxytamoxifen. In either case, p53 activation triggered apoptosis that was not inhibited by the presence of macromolecular synthesis inhibitors. This p53-induced, transcription-independent apoptosis is Bax dependent, proceeds in the absence of a nucleus, and involves Bax translocation and cytochrome c release. Hence, pharmacologic p53 modulators can activate a transcription-independent apoptotic program.

Topics: Animals; Apoptosis; Aza Compounds; bcl-2-Associated X Protein; Bridged Bicyclo Compounds, Heterocyclic; Cell Nucleus; Cells, Cultured; Cloning, Molecular; Cytochromes c; Fibroblasts; Humans; Mice; Mitochondria; Mutation; Protein Synthesis Inhibitors; Protein Transport; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Recombinant Fusion Proteins; Tamoxifen; Transcription, Genetic; Tumor Cells, Cultured; Tumor Suppressor Protein p53

2003