The effect of taurolidine on brain tumor cells.
BACKGROUND
Although an inhibiting effect of the antibacterial substance taurolidine on several tumor cell lines was suggested in 1990, no specific research has been performed concerning its effect on brain tumor cells.


METHODS
Monolayers of rat-derived C6 glioma, mouse-derived HT22 neuronal tumor, and human-derived U373 astrocytoma/glioblastoma cell lines were cultured and incubated with 1 microg/ml to 4 mg/ml of taurolidine. Neuronal and glial brain cells were obtained from rat fetuses at day 15 of gestation and incubated with taurolidine to investigate its effect on normal brain cells.


RESULTS
Following incubation with taurolidine, the tumor cells started to shrink and to become denser. Ultrastructurally, shrinkage of cytoplasm and condensation and marginalization of chromatin could be observed. Exposure to taurolidine at concentrations of 2.8 microg/ml to 2 mg/ml led to cell death of the evaluated tumor cell types. Results of flow cytometry suggested a fragmentation of DNA. Phosphatidylserine expression increased from 6% to 25% following exposure to taurolidine at a concentration of 25 microg/ml. Normal brain cells did not show any significant changes following incubation with taurolidine.


CONCLUSIONS
The characteristics identified by light and electron microscopy and the data obtained by flow cytometry indicate an apoptotic mechanism of cell death via currently unknown pathways. Taurolidine was found to have a direct and selective antineoplastic effect on glial and neuronal brain tumor cells in vitro.
Stendel
Ruediger
R
Department of Neurosurgery, Benjamin Franklin Medical Center, Free University of Berlin, Germany. stendel@medizin.fu-berlin.de
Stoltenburg-Didinger
Gisela
G
Al Keikh
Claudia Lotte
CL
Wattrodt
Michaela
M
Brock
Mario
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D010718:Phosphatidylserines / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013829:Thiadiazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010718:Phosphatidylserines; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine