Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase‐plasminogen activator and matrix metalloproteinase‐2
- 26 May 2004
- journal article
- research article
- Published by Wiley in Molecular Carcinogenesis
- Vol. 40 (3), 143-149
- https://doi.org/10.1002/mc.20018
Abstract
Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Silibinin is a flavonoid antioxidant and wildly used for its antihepatotoxic properties and recent studies have revealed pleiotropic anticancer and antiproliferative capabilities of silibinin. In this study, we first observed that silibinin exerted a dose- and time-dependent inhibitory effect on the invasion and motility, but hardly on the adhesion, of highly metastatic A549 cells in the absence of cytotoxicity. To look at the precise involvement of silibinin in cancer metastasis, A549 cells were treated with silibinin at various concentrations, up to 100 μM, for a defined period and then subjected to gelatin zymography, casein zymography and Western blot to investigate the impacts of silibinin on metalloproteinase-2 (MMP-2), urokinase plasminogen activator (u-PA), and tissue inhibitor of metalloproteinase-2 (TIMP-2), respectively. The results showed that a silibinin treatment may decrease the expressions of MMP-2 and u-PA in a concentration- and time-dependent manner and enhance the expression of TIMP-2. Further analysis with semi-quantitative RT-PCR showed that silibinin may regulate the expressions of MMP-2 and u-PA on the transcriptional level while on the translational or post-translational level for TIMP-2.Keywords
This publication has 29 references indexed in Scilit:
- Flavonoid Antioxidant Silymarin and Skin CancerAntioxidants and Redox Signaling, 2002
- Discoidin Domain Receptor 2 Regulates Fibroblast Proliferation and Migration through the Extracellular Matrix in Association with Transcriptional Activation of Matrix Metalloproteinase-2Published by Elsevier BV ,2002
- Inhibitory Effect of Selenite on Invasion of HT1080 Tumor CellsPublished by Elsevier BV ,2001
- Anti-Angiogenic Potential of a Cancer Chemopreventive Flavonoid Antioxidant, Silymarin: Inhibition of Key Attributes of Vascular Endothelial Cells and Angiogenic Cytokine Secretion by Cancer Epithelial CellsBiochemical and Biophysical Research Communications, 2000
- Modulation of Mitogen-Activated Protein Kinase Activation and Cell Cycle Regulators by the Potent Skin Cancer Preventive Agent SilymarinBiochemical and Biophysical Research Communications, 1999
- Integrin SignalingScience, 1999
- Gene transfer of tissue inhibitor of metalloproteinase-2 inhibits metalloproteinase activity and neointima formation in human saphenous veinsGene Therapy, 1998
- A Synthetic Peptide from Fibronectin Inhibits Experimental Metastasis of Murine Melanoma CellsScience, 1986
- BIOCHEMICAL INTERACTIONS OF TUMOR CELLS WITH THE BASEMENT MEMBRANEAnnual Review of Biochemistry, 1986
- Comparative electrophoretic analysis of human and porcine plasminogen activators in sds-polyacrylamide gels containing plasminogen and caseinBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1983