| Overexpression of acid sphingomyelinase sensitizes glioma cells to chemotherapy. | |
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MedLine Citation:
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PMID: 17576160 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ceramide has been shown by many studies to induce apoptosis. Therefore, upregulation of ceramide is discussed as a novel approach for tumor treatment. However, it is unknown whether overexpression of acid sphingomyelinase releasing ceramide from sphingomyelin sensitizes cells to chemotherapy and, thus, serves as a potential target to amplify chemotherapy. Here, the authors demonstrate that transfection of human or murine glioma cells with acid sphingomyelinase results in a marked sensitization of glioma cells to gemcitabine and doxorubicin, respectively. Transfected cells responded to chemotherapy with an increased activation of acid sphingomyelinase, elevated ceramide levels, and approximately fourfold higher rates of cell death than control transfected cells. Neutralization of reactive oxygen species prevented these events. The data indicate a significant sensitization of glioma cells to chemotherapy treatment by expression of acid sphingomyelinase and further suggest an activation of acid sphingomyelinase by gemcitabine or doxorubicin, respectively, via reactive oxygen species. |
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Authors:
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Georgios Grammatikos; Volker Teichgräber; Alexander Carpinteiro; Tanja Trarbach; Michael Weller; Ulrich R Hengge; Erich Gulbins |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 9 ISSN: 1523-0864 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-06 Completed Date: 2007-10-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 1449-56 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Brain Neoplasms Cell Death / drug effects Cell Line, Tumor Ceramides / metabolism Deoxycytidine / analogs & derivatives, pharmacology Doxorubicin / pharmacology Gene Expression Regulation, Neoplastic Glioma Humans Sphingomyelin Phosphodiesterase / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Ceramides; 103882-84-4/gemcitabine; 23214-92-8/Doxorubicin; 951-77-9/Deoxycytidine; EC 3.1.4.12/Sphingomyelin Phosphodiesterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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