1-furan-2-yl-3-pyridin-2-yl-propenone inhibits the invasion and migration of HT1080 human fibrosarcoma cells through the inhibition of proMMP-2 activation and down regulation of MMP-9 and MT1-MMP.

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.

• Authors: Byung Chul Park, Dinesh Thapa, Yoon-Seok Lee, Mi-Kyoung Kwak, Eung-Seok Lee, Han Gon Choi, Chul Soon Yong, Jung-Ae Kim
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 567 Issue 3 Pg. 193-7 (Jul 19 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17507007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-furan-2-yl-3-pyridin-2-yl-propenone
• Enzyme Precursors
• Furans
• Pyridines
• RNA, Messenger
• Tissue Inhibitor of Metalloproteinase-1
• Gelatinases
• Metalloendopeptidases
• progelatinase
• Matrix Metalloproteinase 9
• Matrix Metalloproteinase 14
• Tetradecanoylphorbol Acetate
• Propane

Topics

• Blotting, Western
• Cell Line, Tumor
• Cell Movement (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Enzyme Activation (drug effects)
• Enzyme Precursors (antagonists & inhibitors)
• Enzyme-Linked Immunosorbent Assay
• Furans (pharmacology)
• Gelatinases (antagonists & inhibitors)
• Humans
• Matrix Metalloproteinase 14 (biosynthesis)
• Matrix Metalloproteinase 9 (biosynthesis)
• Metalloendopeptidases (antagonists & inhibitors)
• Neoplasm Invasiveness (pathology, prevention & control)
• Propane (analogs & derivatives, pharmacology)
• Pyridines (pharmacology)
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tetradecanoylphorbol Acetate (pharmacology)
• Tissue Inhibitor of Metalloproteinase-1 (biosynthesis)
• Wounds and Injuries (pathology)