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Publication Type : Journal Article
Publisher : European Journal of Pharmacology
Source : European Journal of Pharmacology, Volume 893, p.173808 (2021)
Keywords : A549 Cells, Active Transport, Cell Nucleus, Antineoplastic Agents, Phytogenic, Cell Movement, cell proliferation, Disaccharides, Down-Regulation, fibrosarcoma, Gene Expression Regulation, Neoplastic, Humans, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Neoplasm Invasiveness, NF-kappa B, quercetin, signal transduction, Spheroids, Cellular
Campus : Amritapuri
School : School of Biotechnology
Center : Cell Biology
Department : biotechnology
Year : 2021
Abstract : 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.
Cite this Research Publication : Shaji Sanu K., G. Drishya, Damu Sunilkumar, Nanjan Pandurangan, Dr. Geetha Kumar, and Dr. Bipin G. Nair, “Nuclear factor-κB plays an important role in Tamarixetin-mediated inhibition of matrix metalloproteinase-9 expression.”, European Journal of Pharmacology, vol. 893, p. 173808, 2021.