1. Oroxylin A inhibits matrix metalloproteinase-2/9 expression and activation by up-regulating tissue inhibitor of metalloproteinase-2 and suppressing the ERK1/2 signaling pathway.
- Author
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Lu Z, Lu N, Li C, Li F, Zhao K, Lin B, and Guo Q
- Subjects
- Animals, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic isolation & purification, Antineoplastic Agents, Phytogenic therapeutic use, Blotting, Western, Cell Adhesion drug effects, Cell Movement drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Enzyme Activation, Flavonoids chemistry, Flavonoids isolation & purification, Flavonoids therapeutic use, Humans, Matrix Metalloproteinase 2 genetics, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 metabolism, Melanoma, Experimental drug therapy, Mice, Mice, Inbred C57BL, Molecular Structure, Plant Roots chemistry, Real-Time Polymerase Chain Reaction, Scutellaria baicalensis chemistry, Transcription, Genetic, Up-Regulation, Xenograft Model Antitumor Assays, Antineoplastic Agents, Phytogenic pharmacology, Flavonoids pharmacology, MAP Kinase Signaling System drug effects, Matrix Metalloproteinase Inhibitors, Tissue Inhibitor of Metalloproteinase-2 biosynthesis
- Abstract
Matrix metalloproteinases (MMPs) play important roles in the invasion and migration of cancer cells. In this study, we used in vitro and in vivo assays to examine the inhibitory effects of oroxylin A, one of the main bioactive flavonoid extracted from Scutellaria radix, on the human breast carcinoma cell MDA-MB-231 invasion and migration. We found that oroxylin A can suppress cell adhesion, invasion and migration in a concentration-dependent manner. Moreover, oroxylin A led to the reduction of the activity and expression levels of MMP-2 and MMP-9 in gelatin zymography, real-time PCR and western blotting analysis. Further elucidation of the mechanism revealed that oroxylin A increased the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2), the endogenous inhibitor of MMP-2, and repressed the phorbol-12-myristate-13-acetate (PMA)-induced translocation of protein kinase Cδ (PKCδ), phosphorylation of extracellular signal-regulated kinase (ERK1/2) and binding activity of the transcription factor activator protein-1 (AP-1) which are upstream signaling molecules in MMP-9 expression. Our results also indicated that oroxylin A inhibited the lung metastasis of murine melanoma cell B16-F10 in vivo. Therefore, we proposed that oroxylin A might be developed as a therapeutic potential candidate for the treatment of cancer metastasis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
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