Jaceosidin, a pharmacologically active flavone derived from Artemisia argyi, inhibits phorbol-ester-induced upregulation of COX-2 and MMP-9 by blocking phosphorylation of ERK-1 and -2 in cultured human mammary epithelial cells.

Elevated levels of cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) are frequently found in various types of cancerous and transformed cells, with recent studies implicating the upregulation of COX-2 and MMPs in the development of breast cancer. This article investigated the effects of jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone) isolated from Artemisia argyi on the upregulation of COX-2 and MMP-9 induced by the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in MCF10A human breast epithelial cells (MCF10A cells). Treatment of MCF10A cells with TPA induced the upregulation of COX-2 and MMP-9, and this was attenuated by jaceosidin treatment. Jaceosidin also inhibited the invasive and migrative phenotypes of MCF10A cells induced by TPA. Furthermore, jaceosidin blocked the TPA-induced phosphorylation of extracellular signal-regulated protein kinase-1 and -2 (ERK-1 and -2), which is one of the signaling molecules regulating COX-2 and MMP. These results suggest that jaceosidin inhibits the TPA-induced upregulation of COX-2 and MMP-9 by blocking ERK-1 and -2 phosphorylation in human breast epithelial cells, which may be indicative of its chemopreventive potential.