Nuclear factor-κB plays an important role in Tamarixetin-mediated inhibition of matrix metalloproteinase-9 expression
| Autor: | G Drishya, Nanjan Pandurangan, Geetha B. Kumar, Damu Sunilkumar, Sanu K. Shaji, Bipin G. Nair |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Fibrosarcoma Active Transport Cell Nucleus Down-Regulation Endogeny Matrix (biology) Matrix Metalloproteinase Inhibitors medicine.disease_cause Disaccharides 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Cell Movement Spheroids Cellular medicine Humans Neoplasm Invasiveness Clonogenic assay Cell Proliferation Pharmacology NF-kappa B Antineoplastic Agents Phytogenic Cell biology Gene Expression Regulation Neoplastic Tamarixetin 030104 developmental biology chemistry Matrix Metalloproteinase 9 A549 Cells Cancer cell Quercetin Carcinogenesis 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | European journal of pharmacology. 893 |
| ISSN: | 1879-0712 |
| Popis: | Flavonoids possess a broad spectrum of pharmacological properties, including anti-cancer, anti-oxidant and immunomodulatory activities. The current study explored the potential of some less-studied flavonoids in inhibiting Matrix Metalloproteinase-9 (MMP-9), a prominent biomarker, upregulated in a variety of cancers and known to promote migration and invasion of cancer cells. Amongst these, Tamarixetin, a naturally occurring flavonoid derivative of Quercetin, demonstrated significant dose-dependent inhibition of MMP-9 expression. Furthermore, a substantial inhibition of migration, invasion and clonogenic potential of HT1080 cells was also observed in the presence of Tamarixetin, which further suggests its role as a potential anti-cancer agent. It is noteworthy that Tamarixetin inhibits nuclear translocation as well the activity of nuclear factor kappa B (NFκB), both of which are functions essential for the activation of MMP-9 in promoting tumorigenesis. Additionally, the endogenous regulators of MMP-9 that tightly control its activity were also modulated by Tamarixetin, as evident from the 1.9 fold increase in the expression of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), with a concomitant 2.2 fold decrease in Matrix Metalloproteinase-14 (MMP-14) expression. The results obtained were further corroborated in three dimensional (3D) tumor models, which showed significant inhibition of MMP-9 activity as well as reduced invasive potential in the presence of Tamarixetin. Taken together, our observations demonstrate for the first time, the anti-invasive potential of Tamarixetin in cancer cells, indicating its possible use as a template for novel therapeutic applications. |
| Databáze: | OpenAIRE |
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