Article
Cell death induction by betulinic acid, ceramide and TRAIL in primary glioblastoma multiforme cells
Zelltod-Induktion durch Betulinsäure, Ceramide und TRIAL in primären Glioblastomzellen
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Published: | May 4, 2005 |
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Outline
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Objective
Glioblastoma multiforme (WHO Grade IV, GBM) is the most malignant brain tumour with a mean survival time of not seldom less than one year under Standard treatment. Betulinic acid, ceramide and TRAIL (TNF-related apoptosis inducing ligand) represent novel therapeutic agents for potential use in GBM.
Methods
Primary GBM cells of 21 patients with macroscopically complete tumour resection were tested in vitro for cell death induction by betulinic acid, ceramide, TRAIL and established therapeutics (BCNU, cisplatin, doxorubicin, vincristin and gamma-irradiation).
Results
At peak plasma concentrations (PPC), Betulinic acid, ceramide and TRAIL induced cell death in primary GBM cells at higher rates than established cytotoxic drugs. Specific cell death at least or more as 75% was observed in 43% (9=21), 38% (8=21), and 19% (4=21) for betulinic acid, ceramide, and TRAIL respectively, while this was only found in 5% (1=21) of gamma-irradiated and cisplatin-treated cells, and in none of the GBM cultures, where BCNU or vincristin were applied in PPC.
Conclusions
Due to a markedly improved cell death of GBM cells as compared with established therapeutics, Betulinic acid, ceramide and TRAIL might represent potent substances for future treatment of GBM.