Abstract
The activity of the histone deacetylase inhibitor PXD101 was investigated in three hepatocellular carcinoma (HCC) cell lines. PXD101 was found to inhibit cell growth at a dose-dependent manner and induce histone acetylation in PLC/PRF/5, Hep3B and HepG2 cells. In PLC/PRF/5 and Hep3B cells which express hepatitis B-related genes (HBx, HBc and HBc), treatment with PXD101 resulted in apoptosis without a significant effect on viral gene expression. Exposure to PXD101 for up to 48 h had varying effects on the expression of 12 cellular genes with tumor suppressor functions, including p21, SOCS1, CMTM5, RASAL1, DLEC1, SFRP (-1, -2, -4 and -5), ADAMTS (-8 and -9). This study provided the basis for a phase II clinical trial of PXD101 in inoperable hepatitis-B associated HCC.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation / drug effects
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Apoptosis / drug effects
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / pathology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Gene Expression Regulation, Neoplastic / drug effects
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Hepatitis B virus / drug effects
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Hepatitis B virus / genetics
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Histone Deacetylase Inhibitors / pharmacology*
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Histones / metabolism
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Humans
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Hydroxamic Acids / pharmacology*
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sulfonamides
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Histone Deacetylase Inhibitors
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Histones
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Hydroxamic Acids
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RNA, Messenger
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Sulfonamides
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Tumor Suppressor Proteins
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belinostat