Abstract
In this study, we first report the anti-invasive effect of ethylacetate extract from Antrodia cinnamomea (EAC) fruiting bodies in the human liver cancer cell line PLC/PRF/5. Treatment with EAC decreased the cancer invasion of PLC/PRF/5 cells in a dose-dependent manner. This effect was strongly associated with a concomitant decrease in either the level or activity of VEGF, MMP-2, MMP-9 and MT1-MMP, and an increase in the expression of TIMP-1 and TIMP-2. EAC inhibited constitutively activated and inducible NF-kappaB in both its DNA-binding activity and transcriptional activity. Furthermore, EAC also inhibited the TNF-alpha-activated NF-kappaB-dependent reporter gene expression of MMP-9 and VEGF, and the invasion of cancer cells. EAC also exhibited an inhibitory effect on angiogenesis in a Matrigel Plug Angiogenesis Assay. Further investigation revealed that EAC's inhibition of cancer cell growth and invasion was also evident in a nude mice model. Our results indicate that EAC inhibits the activation of NF-kappaB, and may provide a molecular basis for drug development using EAC as an anti-invasive agent in the prevention and treatment of cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetates / chemistry
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Antineoplastic Agents, Phytogenic / pharmacology*
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Biomarkers, Tumor / metabolism
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Carcinoma, Hepatocellular / drug therapy*
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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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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Fruiting Bodies, Fungal / chemistry
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Humans
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Matrix Metalloproteinase 14 / metabolism
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / metabolism
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Neoplasm Invasiveness
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
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Polyporales / chemistry*
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Solvents / chemistry
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Tissue Inhibitor of Metalloproteinase-1 / metabolism
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Tissue Inhibitor of Metalloproteinase-2 / metabolism
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Acetates
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Antineoplastic Agents, Phytogenic
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Biomarkers, Tumor
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NF-kappa B
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Plant Extracts
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Solvents
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Tissue Inhibitor of Metalloproteinase-1
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Tissue Inhibitor of Metalloproteinase-2
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ethyl acetate
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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MMP14 protein, human
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Matrix Metalloproteinase 14