Cell death induction by betulinic acid, ceramide and TRAIL in primary glioblastoma multiforme cells.
BACKGROUND
Glioblastoma multiforme (WHO Grade IV, GBM) is the most malignant brain tumour with a mean survival time of less than one year. 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 > or =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.
Jeremias
I
I
Dr. von Haunersches Kinderspital, Munich, Germany. I.Jeremias@lrz.uni-muenchen.de
Steiner
H H
HH
Benner
A
A
Debatin
K-M
KM
Herold-Mende
C
C
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins; D001932:Brain Neoplasms / Q000473:pathology*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects*; D002518:Ceramides / Q000494:pharmacology*; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008875:Middle Aged; D053978:Pentacyclic Triterpenes; D012189:Retrospective Studies; D053221:TNF-Related Apoptosis-Inducing Ligand; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002518:Ceramides; D008562:Membrane Glycoproteins; D053978:Pentacyclic Triterpenes; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000094062:Betulinic Acid