Metastasis is a major cause of death in
cancer patients. Our previous studies showed that
pinosylvin, a naturally occurring trans-
stilbenoid mainly found in Pinus species, exhibited a potential
cancer chemopreventive activity and also inhibited the growth of various human
cancer cell lines via the regulation of cell cycle progression. In this study, we further evaluated the potential antimetastatic activity of
pinosylvin in in vitro and in vivo models.
Pinosylvin suppressed the expression of
matrix metalloproteinase (MMP)-2, MMP-9 and membrane type 1-MMP in cultured human
fibrosarcoma HT1080 cells. We also found that
pinosylvin inhibited the migration of HT1080 cells in colony dispersion and wound healing assay systems. In in vivo spontaneous pulmonary
metastasis model employing intravenously injected CT26 mouse
colon cancer cells in Balb/c mice,
pinosylvin (10 mg/kg
body weight, intraperitoneal administration) significantly inhibited the formation of
tumor nodules and
tumor weight in lung tissues. The analysis of
tumor in lung tissues indicated that the antimetastatic effect of
pinosylvin coincided with the down-regulation of MMP-9 and
cyclooxygenase-2 expression, and phosphorylation of ERK1/2 and Akt. These data suggest that
pinosylvin might be an effective inhibitor of
tumor cell
metastasis via modulation of
MMPs.