Acteoside inhibits PMA-induced matrix metalloproteinase-9 expression via CaMK/ERK- and JNK/NF-κB-dependent signaling.
Mol Nutr Food Res. 2011 May ;55 Suppl 1:S103-16. Epub 2010 Nov 18. PMID: 21089054
Yong Pil Hwang
SCOPE: Acteoside, an active phenylethanoid glycoside found in bitter tea and many medicinal plants, displays chemopreventive properties. The aim of our study was to determine the effect of acteoside on tumor invasion and migration; the possible mechanisms involved in this inhibition were investigated in human fibrosarcoma HT-1080 cells.
METHODS AND RESULTS: We employed invasion, migration and gelatin zymography assays to characterize the effect of acteoside on HT-1080 cells. Transient transfection assays were performed to investigate gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action. We found that acteoside suppresses phorbol-12-myristate-13-acetate (PMA)-enhanced matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and transcriptional levels through the suppression of NF-κB activation. In addition, acteoside repressed the PMA-induced phosphorylation of ERK1/2 (ERK, extracellular regulated kinase) and JNK1/2. Further, we found that acteoside decreased the PMA-induced influx of Ca(2+) and repressed PMA-induced calmodulin-dependent protein kinase (CaMK) phosphorylation. Furthermore, treatment with BAPTA/AM, W7, or capsazepine markedly decreased PMA-induced MMP-9 secretion and cell migration, as well as ERK and JNK/NF-κB activation.
CONCLUSION: Acteoside inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+) -dependent CaMK/ERK and JNK/NF-κB-signaling pathways. Acteoside therefore has the potential to be a potent anticancer agent in therapeutic strategies for fibrosarcoma metastasis.