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Ceramide metabolism determines glioma cell resistance to chemotherapy


Dumitru, C A; Weller, M; Gulbins, E (2009). Ceramide metabolism determines glioma cell resistance to chemotherapy. Journal of Cellular Physiology, 221(3):688-695.

Abstract

Tumor cell resistance to chemotherapy constitutes a major problem in the treatment of malignant tumors. We here investigated the role of ceramide metabolism for the resistance of glioma cells to treatment with the chemotherapeutic drug, gemcitabine. Gemcitabine triggers a marked release of ceramide in drug-sensitive cells, while glioma cells that are resistant to gemcitabine, fail to accumulate ceramide. While the release of ceramide is very similar in gemcitabine-sensitive and resistant glioma cells upon stimulation, resistant glioma cells rapidly consume ceramide upon gemcitabine treatment or exogenous sphingomyelinase stimulation. Pharmacologic or genetic inhibition of glucosyltransferases prevents ceramide consumption in resistant cells and restores sensitivity of resistant glioma cells to gemcitabine. These data suggest that glioma cell resistance to at least some chemotherapeutic drugs is mediated by rapid consumption of ceramide to prevent cell death.

Abstract

Tumor cell resistance to chemotherapy constitutes a major problem in the treatment of malignant tumors. We here investigated the role of ceramide metabolism for the resistance of glioma cells to treatment with the chemotherapeutic drug, gemcitabine. Gemcitabine triggers a marked release of ceramide in drug-sensitive cells, while glioma cells that are resistant to gemcitabine, fail to accumulate ceramide. While the release of ceramide is very similar in gemcitabine-sensitive and resistant glioma cells upon stimulation, resistant glioma cells rapidly consume ceramide upon gemcitabine treatment or exogenous sphingomyelinase stimulation. Pharmacologic or genetic inhibition of glucosyltransferases prevents ceramide consumption in resistant cells and restores sensitivity of resistant glioma cells to gemcitabine. These data suggest that glioma cell resistance to at least some chemotherapeutic drugs is mediated by rapid consumption of ceramide to prevent cell death.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:16 Nov 2009 09:57
Last Modified:05 Apr 2016 13:33
Publisher:Wiley-Blackwell
ISSN:0021-9541
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:https://doi.org/10.1002/jcp.21907
PubMed ID:19711353

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