| Alkylphosphocholine-induced glioma cell death is BCL-X(L)-sensitive, caspase-independent and characterized by massive cytoplasmic vacuole formation. | |
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MedLine Citation:
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PMID: 15389288 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alkylphosphocholines (APC) are candidate anticancer agents. We here report that APC induce the formation of large vacuoles and typical features of apoptosis in human glioma cell lines, but not in immortalized astrocytes. APC promote caspase activation, poly(ADP-ribose)-polymerase (PARP) processing and cytochrome c release from mitochondria. Adenoviral X-linked inhibitor of apoptosis (XIAP) gene transfer, or exposure to the caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoro-methylketone zVAD-fmk, blocks caspase-7 and PARP processing, but not cell death, whereas BCL-X(L) blocks not only caspase-7 and PARP processing but also cell death. APC induce changes in Delta Psi m in sensitive glioma cells, but not in resistant astrocytes. The changes in Delta Psi m are unaffected by crm-A (cowpox serpin-cytokine response modifier protein A), XIAP or zVAD-fmk, but blocked by BCL-X(L), and are thus a strong predictor of cell death in response to APC. Free radicals are induced, but not responsible for cell death. APC thus induce a characteristic morphological, BCL-X(L)-sensitive, apparently caspase-independent cell death involving mitochondrial alterations selectively in neoplastic astrocytic cells. |
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Authors:
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U Naumann; J Wischhusen; S Weit; J Rieger; H Wolburg; U Massing; M Weller |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell death and differentiation Volume: 11 ISSN: 1350-9047 ISO Abbreviation: Cell Death Differ. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-15 Completed Date: 2005-06-17 Revised Date: 2008-05-14 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 1326-41 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Neuro-Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. ulrike.naumann@uni-tuebingen.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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toxicity* Apoptosis / drug effects*, physiology Astrocytes / drug effects Brain Neoplasms / drug therapy*, pathology, ultrastructure Caspases / drug effects, metabolism* Cell Line, Tumor Collagen Type XI / drug effects, metabolism Cytoplasm / drug effects, pathology, ultrastructure Free Radicals / metabolism Glioma / drug therapy*, pathology, ultrastructure Humans Membrane Potentials / drug effects, genetics Microscopy, Electron, Transmission Mitochondria / drug effects, metabolism Phosphorylcholine / analogs & derivatives*, toxicity* Poly(ADP-ribose) Polymerases Proteins / genetics Proto-Oncogene Proteins c-bcl-2 / drug effects, metabolism* Signal Transduction / drug effects, physiology Stearates / toxicity Vacuoles / drug effects, pathology, ultrastructure X-Linked Inhibitor of Apoptosis Protein bcl-X Protein |
| Chemical | |
Reg. No./Substance:
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0/1-O-phosphocholine-2-O-acetyloctadecane; 0/1-O-phosphocholine-2-O-methyloctadecane; 0/Antineoplastic Agents; 0/BCL2L1 protein, human; 0/COL11A2 protein, human; 0/Collagen Type XI; 0/Free Radicals; 0/Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Stearates; 0/X-Linked Inhibitor of Apoptosis Protein; 0/XIAP protein, human; 0/bcl-X Protein; 107-73-3/Phosphorylcholine; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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