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Cancer Lett ; 295(1): 92-9, 2010 Sep 01.
Article in English | MEDLINE | ID: mdl-20350781

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.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Proliferation/drug effects , NF-kappa B/metabolism , Naphthoquinones/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Apoptosis/drug effects , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Survival/drug effects , Down-Regulation , Enzyme Activation , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Interleukin-6/metabolism , Interleukin-6/pharmacology , MAP Kinase Signaling System/drug effects , Signal Transduction/drug effects , Up-Regulation , X-Linked Inhibitor of Apoptosis Protein/metabolism , bcl-X Protein/metabolism , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
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