The benzoylurea derivative F13 inhibits cell growth, migration and invasion through inducing expression of ERK1/2-mediated RECK in fibrosarcoma HT-1080 cells

Abstract

3-Bromoacetamino-4-methoxy-benzoylurea (F13) is a benzoylurea derivative selected from the library of small molecule tubulin ligands. Our earlier data showed that F13 had lost the capacity to interrupt microtubule dynamics while reserving anticancer activity. In this study, we found that F13 greatly inhibited cell proliferation in various human cancer cells. At concentrations of more than 1 microg/ml, F13 markedly slowed growth and induced apoptosis in HT-1080 cells. This apoptosis occurred through cleavages of caspase 3 and PARP. At low concentrations (< or =1 microg/ml), F13 reduced the migration, adhesion, and invasion of HT-1080 cells. In addition, F13 downregulated the activities of matrix metalloproteinase-2/9 (MMP-2/9) in a culture supernatant. This was found to occur through the upregulation of the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a membrane-anchored inhibitor of MMPs, which acts by reducing ERK1/2 phosphorylation. Our data suggested that F13 might act as a novel RECK inducer, inhibiting cancerous processes with the inactivation of MMP-2/9 by the induction of RECK through the inhibition of ERK1/2 signalling transduction.