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.
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.
Park
Byung Chul
BC
College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan 712-749, South Korea.
Thapa
Dinesh
D
Lee
Yoon-Seok
YS
Kwak
Mi-Kyoung
MK
Lee
Eung-Seok
ES
Choi
Han Gon
HG
Yong
Chul Soon
CS
Kim
Jung-Ae
JA
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D005663:Furans / Q000494:pharmacology*; D018093:Gelatinases / Q000037:antagonists & inhibitors*; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000517:prevention & control*; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000473:pathology
C508534:1-furan-2-yl-3-pyridin-2-yl-propenone; D004792:Enzyme Precursors; D005663:Furans; D011725:Pyridines; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14; D013755:Tetradecanoylphorbol Acetate; D011407:Propane