The cytostatic- and differentiation-inducing effects of cyclopentenyl cytosine on neuroblastoma cell lines

Citation
J. Bierau et al., The cytostatic- and differentiation-inducing effects of cyclopentenyl cytosine on neuroblastoma cell lines, BIOCH PHARM, 62(8), 2001, pp. 1099-1105
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
8
Year of publication
2001
Pages
1099 - 1105
Database
ISI
SICI code
0006-2952(20011015)62:8<1099:TCADEO>2.0.ZU;2-K
Abstract
This paper describes the effects of cyclopentenyl cytosine (CPEC) on the pr oliferation and cell-cycle distribution of the SK-N-BE(2)c and SK-N-SH neur oblastoma. cell lines, as well as their ability to recover from treatment w ith CPEC. The IC50 value of SK-N-BE(2)c for CPEC, determined after 48 hr wa s 80 nM. SK-N-BE(2)c cells showed a time- and concentration-dependent accum ulation in the S-phase of the cell cycle after 2 and 3 days of incubation w ith 50-250 nM CPEC, followed by a G(0)/G(1)-phase arrest after 4 days. Afte r 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 persiste nt 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 greater than or equal to1 muM. SK-N-SH cells incubated with 2 50 nM or I AM CPEC showed a time-dependent accumulation in the S-phase of t he cell cycle, followed by an accumulation in the G(0)/G(1)-phase, which re ached a maximum of 84.1% after 7 days of incubation with 1 muM CPEC. SK-N-S H cells did not resume proliferation after removal of the drug. In addition , CPEC strongly induced differentiation in SK-N-SH cells. After 48 hr incub ation 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. (C) 2001 Elsevier Sci ence Inc. All rights reserved.