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Irigenin, a Novel Lead From Western Himalayan Chemiome Inhibits Fibronectin-Extra Domain A Induced Metastasis in Lung Cancer Cells

Irigenin, a Novel Lead From Western Himalayan Chemiome Inhibits Fibronectin-Extra Domain A Induced Metastasis in Lung Cancer Cells

Asif Amin, Naveed Anjum Chikan, Taseem A Mokhdomi, Shoiab Bukhari, Aabid M Koul, Basit Amin Shah, Fatemeh Rahimi Gharemirshamlu, Asrar H Wafai, Ayub Qadri, Raies A Qadri

Sci Rep. 2016 Nov 16;6:37151.

PMID: 27849000

Abstract:

Several lines of evidence indicate that Fibronectin Extra Domain A (EDA) promotes metastatic capacity of tumor cells by engaging cell surface α9β1 integrins. This interaction mediated by the C-C loop of EDA activates pro-oncogenic signaling pathways leading to epithelial to mesenchymal transition (EMT) of tumor cells, thus signifying its importance in control of metastatic progression. In this context the present study was designed to explore the active compounds from selected ethno-medicinal plants of western Himalayan region for targeting EDA of Fibronectin in lung carcinoma cells. Structure based informatics for drug designing and screening was employed to generate a lead compound(s) feed that were conformationally and energetically viable. Out of 120 compounds selected, Irigenin showed best binding-affinity with C-C loop of EDA. Irigenin specifically targeted α9β1 and α4β1 integrin binding sites on EDA comprising LEU46, PHE47, PRO48, GLU58, LEU59 and GLN60 in its C-C loop as evaluated by energy decomposition per residue of Irigenin-EDA complex. In-vitro cell motility assays complemented with EDA knock-in and knockdown assays distinctively demonstrated that Irigenin prevents metastatic capacity of lung cancer cells by selectively blocking EDA. The results presented thus project Irigenin as a lead compound to overcome Fibronectin EDA induced metastatic progression in lung carcinoma cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP548765	Irigenin		548-76-5	Price

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