Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and In Vivo Invasive Growth Through Targeting C‐Met. (6th January 2016)

• Record Type: Journal Article
• Authors: Ebrahim, Hassan Y.; Elsayed, Heba E.; Mohyeldin, Mohamed M.; Akl, Mohamed R.; Bhattacharjee, Joydeep; Egbert, Susan; El Sayed, Khalid A.
• Is Part Of: Phytotherapy research. Volume 30:Number 4(2016)
• Page Start: 557
• Page End: 566
• Publication Date: 2016-01-06
• Subjects: norstictic acid -- lichen -- c‐Met -- breast cancer -- TNBC -- Usnea; Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.5551
• Languages: English
• ISSNs: 0951-418X

Abstract

Abstract : Breast cancer is a major health problem affecting the female population worldwide. The triple‐negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto‐oncogenic receptor tyrosine kinase c‐Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c‐Met is proposed as a promising candidate target for the control of TNBCs. Lichens‐derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen‐derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer‐guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone‐derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA‐MB‐231 cell proliferation, migration, and invasion, with minimal toxicity to non‐tumorigenic MCF‐10A mammary epithelial cells. Molecular modeling, Z'‐LYTE biochemical kinase assay and Western blot analysis identified c‐Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA‐MB‐231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen‐derived natural products are promising resources to discover novel c‐Met inhibitors useful to control TNBCs. Copyright © 2016 John Wiley & Sons, Ltd.