Rutin as A Novel c-Met Inhibitory Lead for The Control of Triple Negative Breast Malignancies

• Published in: Nutrition and cancer Vol. 69; no. 8; pp. 1256 - 1271
• Main Authors: Elsayed, Heba E., Ebrahim, Hassan Y., Mohyeldin, Mohamed M., Siddique, Abu Bakar, Kamal, Amel M., Haggag, Eman G., El Sayed, Khalid A.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 17-11-2017; Taylor & Francis Ltd
• Subjects: Aberration; Anticancer properties; Antitumor activity; Antitumor agents; Bioassays; Breast cancer; c-Met protein; Cancer; Cell migration; Cell proliferation; Diet; Docking; Flavonoids; Kinases; Lead; Macromolecules; Metastases; Polyphenols; Protein-tyrosine kinase receptors; Rutin; Target recognition; Tyrosine; Xenografts
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2017.1367936

Triple negative breast cancer (TNBC) has high metastatic and mortality potential and lacks effective and selective therapeutic options. Aberrant dysregulation of the receptor tyrosine kinase c-Met promotes TNBC progression, motility and survival and therefore considered a valid therapeutic target. Among various identified anticancer agents, plant polyphenols (PPs) including flavonoids, have been shown to be safe and proven for their antitumor activity through modulating diverse macromolecular targets. This study reports the bioassay-guided identification of the common flavonol glycoside rutin as breast cancer cell proliferation, migration and invasion inhibitor. The cell free Z′-LYTE kinase assay, Western blot and in silico docking experiments uncovered, for the first time, c-Met kinase as a potential mechanistic target for rutin-mediated anticancer effects on TNBC cell lines. Likewise, the intraperitoneal injection of rutin at 30 mg/kg, 3X/week, significantly reduced the growth of the TNBC MDA-MB-231/GFP orthotopic xenograft in nude mouse model. These results clearly designate the functional dietary flavonoid rutin as a potential lead for the prevention and control of c-Met-dependent breast malignancies.