Suppression of PMA-induced tumor cell invasion by capillarisin via the inhibition of NF-kappaB-dependent MMP-9 expression

Abstract

Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of capillarisin, a bioactive flavonoid of Artemisia capillaries, on phorbol myristate acetate (PMA)-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Capillarisin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7 and the Matrigel invasion assay showed that capillarisin reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB-dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the major endogenous inhibitors of MMPs. These results suggest that capillarisin represents a potential anti-metastatic agent suppressing cancer cell invasion through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.