Abstract
Matrix metalloproteinases (MMPs) play important roles in solid tumor invasion and migration. In this study, we showed that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) dose-dependently inhibited HT1080 cell invasion and migration, and decreased MMP-2 and MMP-9 activities. Furthermore, FPP-3 reduced MMP-2 expression at protein and mRNA levels, and suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced expression of MT1-MMP without changing tissue inhibitors of metalloproteinase (TIMP)-2 level. FPP-3 also suppressed TPA-induced increases in MMP-9 protein and mRNA levels, but did not alter TIMP-1 level. Our results suggest that FFP-3 may be a valuable anti-invasive drug candidate for cancer therapy by suppressing MMP-2, MMP-9, and MT1-MMP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line, Tumor
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Cell Movement / drug effects*
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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Enzyme Activation / drug effects
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Enzyme Precursors / antagonists & inhibitors*
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Enzyme-Linked Immunosorbent Assay
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Furans / pharmacology*
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Gelatinases / antagonists & inhibitors*
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Humans
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Matrix Metalloproteinase 14 / biosynthesis*
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Matrix Metalloproteinase 9 / biosynthesis*
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Metalloendopeptidases / antagonists & inhibitors*
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Neoplasm Invasiveness / pathology*
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Neoplasm Invasiveness / prevention & control*
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Propane / analogs & derivatives*
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Propane / pharmacology
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Pyridines / pharmacology*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Tetradecanoylphorbol Acetate / pharmacology
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Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
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Wounds and Injuries / pathology
Substances
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1-furan-2-yl-3-pyridin-2-yl-propenone
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Enzyme Precursors
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Furans
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Pyridines
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RNA, Messenger
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Tissue Inhibitor of Metalloproteinase-1
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Gelatinases
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Metalloendopeptidases
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progelatinase
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Matrix Metalloproteinase 9
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Matrix Metalloproteinase 14
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Tetradecanoylphorbol Acetate
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Propane