The Ethanolic Extract of Bark from Salix Aegyptiaca L. Inhibits the Metastatic Potential and Epithelial to Mesenchymal Transition of Colon Cancer Cell Lines

Abstract

Willow bark extracts have been used for centuries as a natural pain killer. Recently their potential as anticancer agents has been reported. We have shown the high antioxidant activity, phenolic and flavonoid content in the ethanolic extract of bark (EEB) from Salix aegyptiaca, a species endogenous to the Middle East. We have also reported that incubation with EEB resulted in a reduction in cell proliferation through the induction of apoptosis and cell cycle arrest via the inhibition of phosphatidyl inositol 3-kinase/Protein kinase B and mitogen activated protein kinases signaling pathways as strongly as commercial inhibitors. The current study demonstrates the robust inhibition of anchorage-independent growth, motility, migration, and adhesion of colon cancer cell lines HCT-116 and HT-29 by EEB. These in vitro functional changes were accompanied by a restoration of E-cadherin expression, a reduction in EGFR, SNAI1, SNAI2, and Twist1 and the matrix metalloproteases MMP9 and MMP2. Many of these proteins are involved in the process of epithelial to mesenchymal transition, which is considered as a critical step in the progression of noninvasive tumor cells into malignant, metastatic carcinomas. We therefore propose that EEB from Salix aegyptiaca is a potent nutraceutical causing cancer chemoprevention by inhibiting epithelial to mesenchymal transition and can be consumed for its health promoting effects.

Additional information

Funding

We thank Dr Ali Güre, at the Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey for sharing resources. The work was funded by METU Scientific Research Fund (Project no. BAP-2008-07-02-05) and the Turkish Academy of Sciences Young Scientist award (TÜBA-GEBİP) to Sreeparna Banerjee. Shabnam Enayat is supported by a TÜBİTAK bursary for international students (TÜBİTAK-BİDEB 2215). We have no conflict of interest. Shabnam Enayat carried out the experiments and wrote the manuscript. Sreeparna Banerjee supervised the research and wrote the manuscript.