ArticlePloS one2013
Glioma cell death induced by irradiation or alkylating agent chemotherapy is independent of the intrinsic ceramide pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Targeting metabolic mechanisms to overcome temozolomide resistance in glioblastoma.Discover oncology · 2026Review
- Drug Resistance: The Role of Sphingolipid Metabolism.International journal of molecular sciences · 2025Review
- Mammalian target of rapamycin inhibition protects glioma cells from temozolomide-induced cell death.Cell death discovery · 2024Article
- Carmofur prevents cell cycle progression by reducing E2F8 transcription in temozolomide-resistant glioblastoma cells.Cell death discovery · 2023Article
- UHPLC-HRMS-based metabolomic and lipidomic characterization of glioma cells in response to anlotinib.Scientific reports · 2023Article
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Activating transcription factor 4 mediates adaptation of human glioblastoma cells to hypoxia and temozolomide.Scientific reports · 2021Article
- The Role of Sphingolipids Metabolism in Cancer Drug Resistance.Frontiers in oncology · 2021Review
- Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate.Biomolecules · 2020Review
- Synthesis, Characterization, andFrontiers in pharmacology · 2020Article
- Review
- Essential role for acid sphingomyelinase-inhibited autophagy in melanoma response to cisplatin.Oncotarget · 2016Article
- Analysis of the expression of Kv10.1 potassium channel in patients with brain metastases and glioblastoma multiforme: impact on survival.BMC cancer · 2015Article
- GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor-associated epilepsy.Glia · 2015Article
- Sphingolipids: key regulators of apoptosis and pivotal players in cancer drug resistance.International journal of molecular sciences · 2014Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimsResistance 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.
methodsMicroarray 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.
resultsInterrogations 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.
conclusionModulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of alkylating chemotherapy or irradiation.
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