Abstract
Naphtho[1,2-b] furan-4,5-dione (NFD) was investigated for its anti-proliferation effect on human hepatocellular carcinoma (HCC), Hep3B, HepG(2), and Huh-7 cells. The effect of NFD on inhibiting proliferation and apoptosis was correlated with up-regulation of pro-apoptotic protein and down-regulation of pro-survival proteins. Remarkably, we found that NFD inhibited the nuclear translocation of NF-kappaB, likely accounting for the down-regulation of pro-survival Bcl-2 family. Furthermore, suppression of p38 MAPK activity by a specific inhibitor significantly rescued the cell proliferation inhibited by NFD. These findings suggest that signaling imbalance between p38 MAPK and NF-kappaB by NFD results in the proliferative inhibition and apoptosis of HCC tumor cells.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology*
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Cell Line, Tumor
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Cell Nucleus / metabolism
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Cell Proliferation / drug effects*
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Cell Survival / drug effects
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Down-Regulation
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Enzyme Activation
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / metabolism
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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MAP Kinase Signaling System / drug effects
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NF-kappa B / metabolism*
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Naphthoquinones / pharmacology*
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Signal Transduction / drug effects
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Up-Regulation
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X-Linked Inhibitor of Apoptosis Protein / metabolism
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bcl-X Protein / metabolism
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Interleukin-6
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NF-kappa B
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Naphthoquinones
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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bcl-X Protein
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naphtho(1,2-b)furan-4,5-dione
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EGFR protein, human
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ErbB Receptors
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases