Histone deacetylase inhibitor BL1521 induces a G1-phase arrest in neuroblastoma cells through altered expression of cell cycle proteins.

Abstract

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.

• Authors: Krista Ouwehand, Annemieke J M de Ruijter, Chris van Bree, Huib N Caron, André B P van Kuilenburg
• Journal: FEBS letters (FEBS Lett) Vol. 579 Issue 6 Pg. 1523-8 (Feb 28 2005) ISSN: 0014-5793 [Print] England
• PMID: 15733867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BL1521
• Cell Cycle Proteins
• Enzyme Inhibitors
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Histone Deacetylases

Topics

• Cell Cycle Proteins (metabolism)
• Cell Line, Tumor
• Cell Nucleus (drug effects, metabolism)
• Cell Survival (drug effects)
• Enzyme Inhibitors (pharmacology)
• G1 Phase (drug effects)
• Gene Expression Regulation, Neoplastic
• Histone Deacetylase Inhibitors
• Histone Deacetylases (metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Neuroblastoma (metabolism, pathology)