TY - JOUR
T1 - The cytostatic- and differentiation-inducing effects of cyclopentenyl cytosine on neuroblastoma cell lines
AU - Bierau, J.
AU - van Gennip, A. H.
AU - Helleman, J.
AU - van Kuilenburg, A. B.
PY - 2001
Y1 - 2001
N2 - This paper describes the effects of cyclopentenyl cytosine (CPEC) on the proliferation and cell-cycle distribution of the SK-N-BE(2)c and SK-N-SH neuroblastoma cell lines, as well as their ability to recover from treatment with CPEC. The IC50 value of SK-N-BE(2)c for CPEC, determined after 48 hr was 80 nM. SK-N-BE(2)c cells showed a time- and concentration-dependent accumulation in the S-phase of the cell cycle after 2 and 3 days of incubation with 50-250 nM CPEC, followed by a G0/G1-phase arrest after 4 days. After incubation with 50 nM CPEC for 2 days, SK-N-BE(2)c cells fully recovered and resumed logarithmic proliferation. In contrast, a complete and persistent growth arrest occurred when SK-N-BE(2)c cells were incubated for 2 days with 100 or 250 nM CPEC. The IC50 value of SK-N-SH, determined after 48 hr, for CPEC was > or =1 microM. SK-N-SH cells incubated with 250 nM or 1 microM CPEC showed a time-dependent accumulation in the S-phase of the cell cycle, followed by an accumulation in the G0/G1-phase, which reached a maximum of 84.1% after 7 days of incubation with 1 microM CPEC. SK-N-SH cells did not resume proliferation after removal of the drug. In addition, CPEC strongly induced differentiation in SK-N-SH cells. After 48 hr incubation with 250 nM CPEC, 90% of the cell population was differentiated. Both neuronal type and Schwannian type cells were observed. We conclude that at very low concentrations, CPEC has profound cytostatic- and differentiation-inducing effects on the neuroblastoma cells studied
AB - This paper describes the effects of cyclopentenyl cytosine (CPEC) on the proliferation and cell-cycle distribution of the SK-N-BE(2)c and SK-N-SH neuroblastoma cell lines, as well as their ability to recover from treatment with CPEC. The IC50 value of SK-N-BE(2)c for CPEC, determined after 48 hr was 80 nM. SK-N-BE(2)c cells showed a time- and concentration-dependent accumulation in the S-phase of the cell cycle after 2 and 3 days of incubation with 50-250 nM CPEC, followed by a G0/G1-phase arrest after 4 days. After incubation with 50 nM CPEC for 2 days, SK-N-BE(2)c cells fully recovered and resumed logarithmic proliferation. In contrast, a complete and persistent growth arrest occurred when SK-N-BE(2)c cells were incubated for 2 days with 100 or 250 nM CPEC. The IC50 value of SK-N-SH, determined after 48 hr, for CPEC was > or =1 microM. SK-N-SH cells incubated with 250 nM or 1 microM CPEC showed a time-dependent accumulation in the S-phase of the cell cycle, followed by an accumulation in the G0/G1-phase, which reached a maximum of 84.1% after 7 days of incubation with 1 microM CPEC. SK-N-SH cells did not resume proliferation after removal of the drug. In addition, CPEC strongly induced differentiation in SK-N-SH cells. After 48 hr incubation with 250 nM CPEC, 90% of the cell population was differentiated. Both neuronal type and Schwannian type cells were observed. We conclude that at very low concentrations, CPEC has profound cytostatic- and differentiation-inducing effects on the neuroblastoma cells studied
U2 - https://doi.org/10.1016/S0006-2952(01)00756-0
DO - https://doi.org/10.1016/S0006-2952(01)00756-0
M3 - Article
C2 - 11597578
SN - 0006-2952
VL - 62
SP - 1099
EP - 1105
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 8
ER -