2',3'-Dideoxycytidine is a potent inducer of apoptosis in glioblastoma cells.
The effect of 2',3'-dideoxycytidine (ddC) treatment on two human glioblastoma cell lines was characterized. ddC treatment (10 nM-100 microM) of glioblastoma cells was associated with enlargement and shortening of processes within 2-3 days. Assessment of mitochondrial membrane potential showed an early decrease in the number of polarized mitochondria in the glioma cells, at between 16 to 84% of the untreated control. With chronic exposure to varying doses of ddC, the tumor cells underwent apoptosis within 5-32 days. This apoptosis was dramatic, with a complete loss of cell viability in < 6 hours after cells were noted to begin detaching from the tissue culture flask. Supplementation with uridine, pyruvate and glucose could delay cellular death at the lower doses of ddC (10 nM to 15 microM) but not at the higher doses. However, regardless of supplementation, all cells eventually underwent apoptosis. ddC is a potent inducer of apoptosis in human glioblastoma cells. Assessments of efficacy in in vivo models and clinical trials should be performed to determine the value of ddC in the treatment of malignant brain tumors.
Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.
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E
Ullyatt
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BC
Liang
D000963:Antimetabolites / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma; D006801:Humans; D007700:Kinetics; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016047:Zalcitabine / Q000633:toxicity*
D000963:Antimetabolites; D016047:Zalcitabine