TY - JOUR
T1 - Cyclopentenyl cytosine primes SK-N-BE(2)c neuroblastoma cells for cytarabine toxicity
AU - Bierau, Jörgen
AU - van Gennip, Albert H.
AU - Leen, René
AU - Helleman, Jozien
AU - Caron, Huib N.
AU - van Kuilenburg, André B. P.
PY - 2003
Y1 - 2003
N2 - 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
AB - 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
U2 - https://doi.org/10.1002/ijc.10858
DO - https://doi.org/10.1002/ijc.10858
M3 - Article
C2 - 12471622
SN - 0020-7136
VL - 103
SP - 387
EP - 392
JO - International journal of cancer. Journal international du cancer
JF - International journal of cancer. Journal international du cancer
IS - 3
ER -