Document Detail


Overexpression of acid sphingomyelinase sensitizes glioma cells to chemotherapy.
MedLine Citation:
PMID:  17576160     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Georgios Grammatikos; Volker Teichgräber; Alexander Carpinteiro; Tanja Trarbach; Michael Weller; Ulrich R Hengge; Erich Gulbins
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  9     ISSN:  1523-0864     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-06     Completed Date:  2007-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1449-56     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / 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:
0/Antineoplastic Agents; 0/Ceramides; 103882-84-4/gemcitabine; 23214-92-8/Doxorubicin; 951-77-9/Deoxycytidine; EC 3.1.4.12/Sphingomyelin Phosphodiesterase

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