Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-κB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells

Anisomeles indica popularly known in Taiwan as 'yu-chen-tsao' has been traditionally used as an anticancer and anti-inflammatory agent; however, little is known about its anti-metastatic potential. Therefore, we attempted in this study to examine the anti-metastatic potential of A. indica aqueous extract (AI), its isolated compounds apigenin, ovatodiolide, β-sitosterol and acteoside in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced human breast adenocarcinoma MCF-7 cells. Among the test agents, crude extract AI and pure compound apigenin potently suppressed the TPA-induced MCF-7 cells migration and invasion. In addition, AI and apigenin time- and dose-dependently down regulated the matrix metalloproteinase (MMP)-9 enzymatic activities and its mRNA expression. Furthermore, AI and apigenin also down regulated the nuclear factor (NF)-κB subunit p65, and activator protein (AP)-1 subunit c-Fos proteins expression in nucleus and, transcriptional activity of NF-κB and AP-1. This is the first report on the anti-metastatic potential of A. indica that suppressed the cancer cell invasion through the inhibition of MMP-9 enzyme via NF-κB/AP-1 signaling. Taken together, our data indicate that A. indica can be considered as a source of new anti-metastatic agent for food and pharmaceutical industries.