Abstract
Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh-7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh-7. It inhibited cell proliferation in vitro and induced G(0)/G(1) arrest in HepG2 and apoptosis in Huh-7. Gene expression of liver-specific functions and liver-enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh-7. Our results indicate that TSA can induce cell-cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines.
Copyright 2002 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Albumins / metabolism
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Ammonia / metabolism
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Apoptosis / drug effects*
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Carcinoma, Hepatocellular / enzymology
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Carcinoma, Hepatocellular / pathology*
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Cell Cycle / drug effects
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology*
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Gene Expression Regulation, Neoplastic
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Hepatocytes / drug effects*
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Hepatocytes / metabolism
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Histone Deacetylase Inhibitors*
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Histones / metabolism
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Humans
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Hydroxamic Acids / pharmacology*
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Liver Neoplasms / enzymology
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Liver Neoplasms / pathology*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / enzymology
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Tumor Cells, Cultured / pathology
Substances
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Albumins
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Histones
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Hydroxamic Acids
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Neoplasm Proteins
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trichostatin A
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Ammonia