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 rnetalloproteinases (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 NIMP-2 and MMP-9 activities. Furtherniore. FPP-3 reduced MMP-2 expression at protein and inRNA levels, and suppressed 12-0-tetradecanoylphorbol-13-acetate (TPA)enhanced expression of MTl-MMP without changing tissue inhibitors of rnetalloproteinase (TIMP)-2 level. FPP-3 also suppressed TPA-induced increases in MMP-9 protein and rnRNA 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. (C) 2007 Elsevier B.V. All rights reserved.