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

Nutrition and Cancer
Heba E ElsayedKhalid A El Sayed

Abstract

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.

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Citations

Apr 24, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Sarmistha Mitra, Raju Dash
Dec 16, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nilesh MalaviaSanyog Jain
Apr 28, 2020·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Rama Rao MallaVenkata Ramesh Dasari
Sep 17, 2020·European Journal of Medicinal Chemistry·Rajibul Islam, Kok Wai Lam
Apr 20, 2021·Toxicological Research·Stephen SafeRupesh Shrestha
Oct 16, 2020·Critical Reviews in Food Science and Nutrition·Arakkaveettil Kabeer FarhaHarold Corke
May 18, 2021·Chemistry & Biodiversity·Han ChenXiaoling Lu
Oct 30, 2021·Drug Discovery Today·Shivangi AgarwalSushil K Kashaw

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Methods Mentioned

BETA
xenograft
NMR
Assay
X-ray
GTPase
glycosylation

Software Mentioned

LigPrep
NMR
GraphPad Prism
GraphPad
Maestro
Schrödinger

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