Ouwehand Krista, de Ruijter Annemieke J M, van Bree Chris, Caron Huib N, van Kuilenburg André B P
Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
FEBS Lett. 2005 Feb 28;579(6):1523-8. doi: 10.1016/j.febslet.2005.01.058.
Histone deacetylase inhibitors (HDACi) have been discovered as potential drugs for cancer treatment. The effect of BL1521, a novel HDACi, on the cell cycle distribution and the induction of apoptosis was investigated in a panel of MYCN single copy and MYCN amplified neuroblastoma cell lines. BL1521 arrested neuroblastoma cells in the G1 phase and induced up to 30% apoptosis. Downregulation of CDK4, upregulation of p21(WAF1/CIP1) and an increase of hypophosphorylated retinoblastoma protein were observed, indicating a possible mechanism for the cell-cycle arrest. BL1521 also induced downregulation of p27, which may underlie the observed induction of apoptosis.
组蛋白去乙酰化酶抑制剂（HDACi）已被发现是潜在的癌症治疗药物。在一组MYCN单拷贝和MYCN扩增的神经母细胞瘤细胞系中，研究了新型HDACi BL1521对细胞周期分布和凋亡诱导的影响。BL1521使神经母细胞瘤细胞停滞于G1期，并诱导高达30%的细胞凋亡。观察到细胞周期蛋白依赖性激酶4（CDK4）下调、p21（WAF1/CIP1）上调以及低磷酸化视网膜母细胞瘤蛋白增加，这表明细胞周期停滞的一种可能机制。BL1521还诱导p27下调，这可能是观察到的凋亡诱导的基础。
