Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells.
BACKGROUND
Human malignant gliomas are resistant to chemotherapy. Here, we examine the modulation of drug-induced cytotoxicity and clonogenic cell death of glioma cells by antioxidants.


METHODS
We studied the effects on drug toxicity of three structurally unrelated antioxidants, N-acetylcysteine, superoxide dismutase or phenyl-N-tert-butyl-alpha-phenylnitrone, in acute cytotoxicity and clonogenic cell death assays in LN-18, LN-229 and T98G cells. Two fluorescent dyes, 2',7'-dichlorodihydroJluorescein diacetate (DCF-Hr2) and dihydro-rhodamine-123, were used to monitor free radical formation after drug exposure.


RESULTS
The antioxidants inhibited acute cytotoxicity and clonogenic cell death induced by cisplatin in all cell lines but had little effect on the toxicity of BCNU, doxorubicin, VM26, vincristine, cytarabine or camptothecin. Cisplatin toxicity was not associated with free radical formation and was not potentiated by L-buthionine-[S,R]-sulfoximine-induced glutathione depletion.


CONCLUSIONS
Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells in the absence of drug-induced free radical formation.
Roller
A
A
Department of Neurology, University of Tübingen, School of Medicine, Germany.
Weller
M
M
D000111:Acetylcysteine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003497:Cyclic N-Oxides; D004317:Doxorubicin / Q000633:toxicity; D005456:Fluorescent Dyes; D005609:Free Radicals / Q000378:metabolism; D005910:Glioma; D006801:Humans; D009589:Nitrogen Oxides / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D005456:Fluorescent Dyes; D005609:Free Radicals; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D004317:Doxorubicin; D013482:Superoxide Dismutase; D002945:Cisplatin; D000111:Acetylcysteine