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Cyclopentenyl cytosine primes SK-N-BE(2)c neuroblastoma cells for cytarabine toxicity by Jörgen Bierau; Albert H. van Gennip; René Leen; Jozien Helleman; Huib N. Caron; André B.P. van Kuilenburg is a Medicine article available to read on EtoBox.
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## Abstract CPEC is a potent inhibitor of CTP synthetase and causes 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 (50–250 nM) and AraC (37.5–500 nM) decreased the 4‐day ED~50~ 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 ED~50~ 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 [^3^H]AraC increased the total amount of AraC nucleotides and incorporation of [^3^H]AraC into DNA by 392% and 337%, respectively, compared to non‐CPEC‐treated cells. When 20 nM [^3^H]AraC was used, the maximum incorporation of [^3^H]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
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- Author
- Jörgen Bierau; Albert H. van Gennip; René Leen; Jozien Helleman; Huib N. Caron; André B.P. van Kuilenburg
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)
- Published
- 2002
- Language
- EN
- Field
- Medicine (Health Sciences)