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Fas (APO-1/CD95) signaling pathway is intact in radioresistant human glioma cells
G L Yount1, K S Levine, H Kuriyama
1Preuss Laboratory for Molecular Neuro-oncology, Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco, 94143, USA.
Abstract:
Radiation-induced apoptosis can be mediated through pathways initiated by either DNA damage or ceramide-induced Fas signaling. Glioblastoma multiforme is a primary brain tumor that is highly resistant to irradiation, and U-87 MG, SF126, and T98G are glioblastoma-derived cell lines that mimic this characteristic. We found that these radioresistant glioma cells are susceptible to Fas-mediated cell death induced by treatment with either anti-Fas antibody or exogenous ceramide. Fas-mediated cell death in these cell lines is p53-independent. These data demonstrate that apoptosis can be induced by ceramide and mediated through the Fas pathway in glioma cells, although high-dose ionizing radiation fails to trigger this pathway.
Insights
Glioblastoma cells resist radiation but can undergo programmed cell death (apoptosis) via the Fas pathway. Ceramide or anti-Fas antibody treatment effectively induces this Fas-mediated apoptosis, independent of p53.
Area of Science:
- Molecular Biology
- Oncology
- Cell Death Research
Background:
- Glioblastoma multiforme is a primary brain tumor known for its resistance to radiation therapy.
- Radiation-induced apoptosis can be triggered by DNA damage or ceramide-mediated Fas signaling.
- U-87 MG, SF126, and T98G are glioblastoma cell lines exhibiting characteristic radioresistance.
Purpose of the Study:
- To investigate the susceptibility of radioresistant glioblastoma cells to Fas-mediated apoptosis.
- To determine if ceramide or anti-Fas antibody can induce cell death in these resistant cell lines.
- To explore the role of the p53 pathway in Fas-mediated cell death in glioma cells.
Main Methods:
- Treatment of glioblastoma cell lines (U-87 MG, SF126, T98G) with anti-Fas antibody.
- Treatment of glioblastoma cell lines with exogenous ceramide.
- Assessment of Fas-mediated cell death and p53-independence.
Main Results:
- The radioresistant glioblastoma cell lines were susceptible to Fas-mediated cell death.
- Treatment with anti-Fas antibody or exogenous ceramide effectively induced apoptosis.
- Fas-mediated cell death in these glioma cells was found to be p53-independent.
Conclusions:
- Apoptosis can be induced by ceramide and mediated through the Fas pathway in glioma cells.
- High-dose ionizing radiation does not effectively trigger the Fas pathway in these radioresistant cells.
- Targeting the Fas pathway presents a potential therapeutic strategy for glioblastoma.