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

• Published in: Annals of the New York Academy of Sciences Vol. 1095; no. 1; pp. 458 - 466
• Main Authors: JEONG, MIN A, LEE, KI WON, YOON, DO-YOUNG, LEE, HYONG JOO
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.01.2007
• Subjects: Artemisia; Cell Line; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 Inhibitors - pharmacology; cyclooxygenase-2; Epithelial Cells - drug effects; Epithelial Cells - enzymology; extracellular signal-regulated protein kinase-1 and -2; Flavonoids - pharmacology; human breast epithelial cells; Humans; invasion; jaceosidin; Mammary Glands, Human - cytology; Mammary Glands, Human - drug effects; Mammary Glands, Human - enzymology; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase Inhibitors; matrix metalloproteinase-9; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; migration; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Phosphorylation - drug effects; Protease Inhibitors - pharmacology; Protein Kinase Inhibitors - pharmacology; Tetradecanoylphorbol Acetate - antagonists & inhibitors; Tetradecanoylphorbol Acetate - pharmacology; Up-Regulation - drug effects
• ISSN: 0077-8923; 1749-6632; 1930-6547
• DOI: 10.1196/annals.1397.049

:  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.