| Role of ceramide during cisplatin-induced apoptosis in C6 glioma cells. | |
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MedLine Citation:
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PMID: 11451199 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cisplatin is commonly used for the treatment of malignant brain tumors. However, the mechanisms of cell death by cisplatin are not fully understood. Therefore, the present study was designed to elucidate the apoptotic signaling pathway(s) activated by cisplatin in a C6 rat glioma cell line. C6 cells were treated with various concentrations of cisplatin (0.2-10 microg/ml) for 24-72 h. At 10 microg/ml cisplatin, over 90% of the cells became dead at 72 h. Apoptotic death was confirmed by condensation and fragmentation of nuclei, and DNA laddering. Even in cells treated with 1.5 microg/ml cisplatin, typical apoptotic cells were observed at 72 h. The intracellular level of ceramide, measured Escherichia coli diacylglycerol kinase markedly increased during 24-72 h after the addition of 10 microg/ml cisplatin. The activity of caspase-3(-like) proteases increased and reached a peak at 48 h. Inhibitors of caspases reduced the number of apoptotic cells. Pretreatment of C6 cells with glutathione or N-acetyl-cysteine, which are known to block the activation of neutral magnesium-dependent sphingomyelinase, inhibited ceramide formation, leading to suppression of both activation of caspase-3(-like) proteases and apoptosis by cisplatin. In contrast, pretreatment of the cells with N-oleoylethanolamine (OE), a ceramidase inhibitor, potentiated apoptosis induced by cisplatin. Furthermore, OE enhanced sensitivity of the cisplatin-resistant cells to cisplatin. These results suggest that ceramide is closely implicated in apoptosis of glioma cells by cisplatin through activation of caspase-3(-like) proteases. |
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Authors:
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S Noda; S Yoshimura; M Sawada; T Naganawa; T Iwama; S Nakashima; N Sakai |
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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: Journal of neuro-oncology Volume: 52 ISSN: 0167-594X ISO Abbreviation: J. Neurooncol. Publication Date: 2001 Mar |
Date Detail:
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Created Date: 2001-07-13 Completed Date: 2001-12-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8309335 Medline TA: J Neurooncol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 11-21 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, Gifu University School of Medicine, Japan. snmag@cc.gifu-u.ac.jp |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Animals Antineoplastic Agents / pharmacology* Apoptosis / physiology* Caspase 3 Caspases / metabolism Ceramides / antagonists & inhibitors, physiology* Cisplatin / pharmacology* Drug Synergism Endopeptidases / metabolism Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Ethanolamines / pharmacology Glioma / physiopathology*, ultrastructure Glutathione / pharmacology Microscopy, Electron Rats Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Ceramides; 0/Enzyme Inhibitors; 0/Ethanolamines; 111-58-0/N-oleoylethanolamine; 15663-27-1/Cisplatin; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; EC 3.4.-/Endopeptidases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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