Inhibitory effect of immature plum on PMA-induced MMP-9 expression in human hepatocellular carcinoma.

The goal of this study was to evaluate the anticancer effect of Prunus salicina Lindl. cv. Soldam at three maturity stages (immature, midmature and mature). In search for anticancer effects of immature plum extract (IPE), we have found its antimigrative property in (phorbol 12-myristate 13-acetate) PMA-induced HepG2 cells, and this effect is associated with inhibition of MMP-9 activity. IPE appeared to have a strong inhibitory effect on the PMA-induced MMP-9 secretion through suppression of the transcriptional activity of the MMP-9 gene independently of the TIMP gene in HepG2 cells. PMA induced the translocation of c-jun and p65 to the nucleus; however, IPE inhibited their nuclear translocations induced by PMA in HepG2 cells. These results clearly indicate that IPE suppresses both AP-1- and NF-kappaB-mediated MMP-9 gene transcriptional activity through inhibiting the nuclear translocations of AP-1 and NF-kappaB. These findings suggest that AP-1 and NF-kappaB activations through the ERK, p38 MAPK and JNK pathways appears to be required for the induction of MMP-9 expression by PMA in IPE, and IPE regulates PMA-stimulated MMP-9 expression by suppressing the p38 MAPK, JNK and ERK pathways. IPE leads to a decrease in the migration potential of HepG2 cells in vitro, and this suggests that the migration inhibition is correlated well with its inhibition of MMP-9 expression.