Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells
Roller, A.; Weller, M.
Anticancer Research 18(6a): 4493-4497
1998
ISSN/ISBN: 0250-7005 PMID: 9891515 Document Number: 496475
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. 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. 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. Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells in the absence of drug-induced free radical formation.