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.
Jeong
Min A
MA
School of Agricultural Biotechnology and Center for Agricultual Biomaterials. Seoul National University, Korea.
Lee
Ki Won
KW
Yoon
Do-Young
DY
Lee
Hyong Joo
HJ
D019306:Artemisia; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D052246:Cyclooxygenase 2 Inhibitors; D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; C477508:jaceosidin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate