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dc.contributor.author
Gramatzki, D.
dc.contributor.author
Herrmann, Caroline
dc.contributor.author
Happold, C.
dc.contributor.author
Becker, K. A.
dc.contributor.author
Gulbins, E.
dc.contributor.author
Weller, Michael
dc.contributor.author
Tabatabai, Ghazaleh
dc.date.accessioned
2018-07-26T12:11:07Z
dc.date.available
2017-06-10T18:14:53Z
dc.date.available
2018-07-26T12:11:07Z
dc.date.issued
2013-05-07
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0063527
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/68332
dc.identifier.doi
10.3929/ethz-b-000068332
dc.description.abstract
Background/Aims Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS) catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells. Methods Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II–IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA) was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ)-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations. Results Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation. Conclusion Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of alkylating chemotherapy or irradiation.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Glioma Cell Death Induced by Irradiation or Alkylating Agent Chemotherapy Is Independent of the Intrinsic Ceramide Pathway
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
8
en_US
ethz.journal.issue
5
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e63527
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
006206116
ethz.publication.place
Lawrence, Kan.
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-10T18:16:52Z
ethz.source
ECIT
ethz.identifier.importid
imp593650b6107b336175
ethz.ecitpid
pub:108538
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T02:10:43Z
ethz.rosetta.lastUpdated
2018-09-01T10:48:26Z
ethz.rosetta.versionExported
true
ethz.COinS
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