Inhibition of matrix degrading enzymes and invasion in human glioblastoma (U87MG) Cells by isoflavones

Glioblastoma multiforme is a primary brain tumor associated with extensive invasion into surrounding brain tissue. Matrix metalloproteinases (MMPs) and urokinase plasminogen activation (uPA) system are shown to be involved in tumor invasion as they help in degradation of extracellular matrix (ECM) p...

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Bibliographic Details
Published in:Journal of neuro-oncology 2006-09, Vol.79 (2), p.135-142
Main Authors: PULI, Shilpa, LAI, James C. K, BHUSHAN, Alok
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain Neoplasms - drug therapy
Brain Neoplasms - enzymology
Cell Line, Tumor
Development. Senescence. Regeneration. Transplantation
Dose-Response Relationship, Drug
Down-Regulation
Enzyme Inhibitors - administration & dosage
Enzyme Precursors - drug effects
Enzyme Precursors - metabolism
Epidermal Growth Factor - metabolism
Extracellular Matrix - metabolism
Fundamental and applied biological sciences. Psychology
Genistein - administration & dosage
Glioblastoma - drug therapy
Glioblastoma - enzymology
Human viral diseases
Humans
Infectious diseases
Matrix Metalloproteinase 2 - drug effects
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 9 - drug effects
Matrix Metalloproteinase 9 - metabolism
Matrix Metalloproteinases - drug effects
Matrix Metalloproteinases - metabolism
Matrix Metalloproteinases, Membrane-Associated
Medical sciences
Neoplasm Invasiveness
Neurology
Receptors, Cell Surface - drug effects
Receptors, Cell Surface - metabolism
Receptors, Urokinase Plasminogen Activator
Vertebrates: nervous system and sense organs
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
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Summary:Glioblastoma multiforme is a primary brain tumor associated with extensive invasion into surrounding brain tissue. Matrix metalloproteinases (MMPs) and urokinase plasminogen activation (uPA) system are shown to be involved in tumor invasion as they help in degradation of extracellular matrix (ECM) proteins and thus assist in the movement of cells. MMP-2 and 9 were shown to be upregulated in gliomas, suggesting their involvement in invasion. Genistein and biochanin A are isoflavones commonly known as phytoestrogens and have some anticancer properties. We hypothesize that these two isoflavones can induce a lowering of tumor invasion by decreasing the activity of matrix degrading enzymes. In this study we investigated the effects of genistein and biochanin A on invasive activity of U87MG cells using the Calbiochem in vitro invasion assay system. Our results suggest that genistein and biochanin A induced a decrease in invasive activity of U87MG cells in a dose-related manner. Genistein also induced a decrease in EGF-stimulated invasion thereby implicating an involvement of EGF-mediated signaling in invasion. Our results also show that treatment of U87MG cells with the two isoflavones induced decreases in the enzymatic activity of MMP-9 and the protein levels of MT1-MMP and uPAR.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-006-9126-0