Cyclopentenyl cytosine primes SK-N-BE(2)c neuroblastoma cells for cytarabine toxicity

Jörgen Bierau, Albert H. van Gennip, René Leen, Jozien Helleman, Huib N. Caron, André B. P. van Kuilenburg

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19 Citations (Scopus)

Abstract

depletion of CTP and dCTP pools. AraC is an analog of dCyd and a chemotherapeutic agent. Here, we demonstrate that, upon incubation with CPEC, both the anabolism and cytostatic effect of AraC in SK-N-BE(2)c neuroblastoma cells were increased. Cotreatment of CPEC (SO-2SO nM) and AraC (37.5-500 nM) decreased the 4-day ED50 value for AraC 2- to 8-fold in the SK-N-BE(2)c cell line, while pretreatment with CPEC followed by incubation with AraC alone decreased the 4-day ED50 value for AraC 1- to 19-fold. Preincubation of SK-N-BE(2)c cells with 100 nM CPEC followed by incubation with 500 nM [H-3]AraC increased the total amount of AraC nucleotides and incorporation of [H-3]AraC into DNA by 392% and 337%, respectively, compared to non-CPEC-treated cells. When 20 nM [H-3]AraC was used the maximum incorporation of [H-3]AraC into DNA was 1,378% compared to non-CPEC-treated cells. Incorporation of AraC into DNA correlated well with the accumulation of cells in S phase of the cell cycle caused by CPEC. DNA synthesis was almost completely inhibited (>91%) when 100 nM CPEC and 500 nM AraC were combined. CPEC alone and the combination of CPEC and AraC increased caspase-3 activity 3-fold, indicating induction of apoptosis in SK-N-BE(2)c cells. In contrast, AraC alone did not induce caspase-3 activity. Our results demonstrate that low concentrations of CPEC profoundly increase the cytostatic properties of AraC toward SK-N-BE(2)c human neuroblastoma cells. (C) 2002 Wiley-Liss, Inc
Original languageEnglish
Pages (from-to)387-392
JournalInternational journal of cancer. Journal international du cancer
Volume103
Issue number3
DOIs
Publication statusPublished - 2003

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