title: Overexpression of acid sphingomyelinase sensitizes glioma cells to chemotherapy.
abstract: 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.affiliation: Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Grammatikos
authors.forename: Volker
authors.initials: V
authors.lastname: Teichgräber
authors.forename: Alexander
authors.initials: A
authors.lastname: Carpinteiro
authors.forename: Tanja
authors.initials: T
authors.lastname: Trarbach
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Hengge
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma; D006801:Humans; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D003841:Deoxycytidine; D004317:Doxorubicin; D013108:Sphingomyelin Phosphodiesterase; D000093542:Gemcitabine