Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression

► MMP-9 plays a pivotal role in the invasion of MCF-7 breast cancer cells. ► TPA stimulates MMP-9 expression through activation of MAPK/NF-κB and MAPK/AP-1 pathways. ► Dihydroavenanthramide D suppresses MMP-9 expression via inhibition of TPA-induced MAPK/NF-κB and MAPK/AP-1 activations. ► Dihydroavenanthramide D blocks cell invasion of MCF-7 breast cancer cells. Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12- O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.