Schematic model of the signaling pathways involved in chrysin inhibiting PMA-induced MMP-9 expression.

PMA stimulates ERK1/2 and JNK1/2 phosphorylation, in turn activating c-Fos and c-Jun, respectively. The phosphorylated c-Fos and c-Jun are translated into the nucleus, where they cooperatively bind to AP-1 binding site, thereby triggering MMP-9 gene expression. The higher level of MMP-9 expression enhances the degradation of the matrix and increases the cell invasiveness. In this model, chrysin acts as an inhibitor of the JNK1/2 and ERK1/2 signaling pathways, and decreases PMA-induced MMP-9 via suppressing AP-1 activation.