Hybrid polar histone deacetylase inhibitor induces apoptosis and CD95/CD95 ligand expression in human neuroblastoma

Inhibitors of histone deacetylase (HDAC) have been shown to have both apoptotic and differentiating effects on various tumor cells. M-carboxycinnamic acid bishydroxamide (CBHA) is a recently developed hybrid polar compound structurally related to hexamethylene bisacetamide. CBHA is a potent inhibito...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1999-09, Vol.59 (17), p.4392-4399
Main Authors: GLICK, R. D, SWENDEMAN, S. L, COFFEY, D. C, RIFKIND, R. A, MARKS, P. A, RICHON, V. M, LA QUAGLIA, M. P
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Biological and medical sciences
Caspase Inhibitors
Cell Division - drug effects
Cell Nucleus - drug effects
Chemotherapy
Cinnamates - pharmacology
Cycloheximide - pharmacology
DNA Fragmentation - drug effects
Enzyme Inhibitors - pharmacology
Fas Ligand Protein
fas Receptor - biosynthesis
Histone Deacetylase Inhibitors
Histones - metabolism
Humans
Medical sciences
Membrane Glycoproteins - biosynthesis
Neuroblastoma - drug therapy
Neuroblastoma - metabolism
Neuroblastoma - pathology
Pharmacology. Drug treatments
Tumor Cells, Cultured
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Summary:Inhibitors of histone deacetylase (HDAC) have been shown to have both apoptotic and differentiating effects on various tumor cells. M-carboxycinnamic acid bishydroxamide (CBHA) is a recently developed hybrid polar compound structurally related to hexamethylene bisacetamide. CBHA is a potent inhibitor of HDAC activity. CBHA induces cellular growth arrest and differentiation in model tumor systems. We undertook an investigation of the effects of CBHA on human neuroblastoma cell lines in vitro. When added to cultures of a panel of neuroblastoma cell lines, CBHA induced the accumulation of acetylated histones H3 and H4, consistent with the inhibition of HDAC. Concentrations of CBHA between 0.5 microM and 4 microM led to apoptosis in nine of nine neuroblastoma cell lines. Apoptosis was assessed by DNA fragmentation analysis and the appearance of a sub-G1 (
ISSN:0008-5472
1538-7445