Dihydrotanshinone-I modulates Epithelial Mesenchymal Transition (EMT) Thereby Impairing Migration and Clonogenicity of Triple Negative Breast Cancer Cells.

Akanksha Kashyap,Chandra Prasad,Arundhathi Dev J R,Sheikh Umar

doi:10.31557/apjcp.2021.22.7.2177

Abstract

Background: Salvia miltiorrhiza Bunge (Danshen), has been used for its therapeutic value in Traditional Chinese Medicine (TCM), for almost a thousand years. Dihydrotanshinone-I (DHTS) is a lipophilic compound isolated from the plant Salvia miltiorrhiza that has been shown to induce anti-proliferative and apoptotic effects on breast cancer cells. In the present study, we investigated the anti-migratory effect of DHTS on TNBC cell lines by studying the Epithelial Mesenchymal Transition (EMT) changes. Methods:IC50 values for DHTS in TNBC breast cancer cells were either discovered by literature search or by performing MTT assay. DHTS effect on EMT markers (viz. CD44, E-cadherin, Vimentin, N-cadherin, and active β-catenin) was studied using western blotting. Association between EMT and migration was further carried out in DHTS treated TNBC cells by wound healing assay. Cancer stemness and proliferation potential were further accessed using colony formation assay.Results:MTT assay revealed IC50 of MDA-MB-468 cells at 2 µM for 24 h. Subsequently, DHTS treatment in TNBC cell lines (MDA-MB-468 and MDA-MB-231) led to decrease in mesenchymal markers i.e. vimentin, N-cadherin and, active β-catenin. DHTS treated MDA-MB-468 cells showed a decrease in adhesion protein CD44 and an increase in epithelial protein E-cadherin. Additionally, a decrease in EMT potential was positively associated with the inhibition of migration and clonogenic potential in DHTS treated TNBC cells. Conclusion:In this study, we have demonstrated for the first time that DHTS has the potential to inhibit the migration and clonogenicity of highly aggressive TNBC cells by obstructing Epithelial to Mesenchymal Transition.

Highlights

Breast cancer is the most common and leading cause of cancer-associated mortality among women worldwide (Coughlin and Ekwueme., 2009; Bray et al, 2018)
Dihydrotanshinone-I (DHTS) is a lipophilic compound isolated from the plant Salvia miltiorrhiza that has been shown to induce anti-proliferative and apoptotic effects on breast cancer cells
We investigated the potential of 15,16-dihydrotanshinone-I (DHTS) for its anti-migratory action in Triple-negative breast cancer (TNBC) cell lines. (DHTS) is an abietane diterpene compound isolated from the medicinal plant Salvia Miltiorrhiza

Summary

Introduction

Breast cancer is the most common and leading cause of cancer-associated mortality among women worldwide (Coughlin and Ekwueme., 2009; Bray et al, 2018). EMT is a fundamental biological phenomenon wherein polarized epithelial cells that are adherent to the basement membrane lose their polarity by undergoing multiple molecular changes to acquire a mesenchymal phenotype (Kalluri and Weinberg., 2010). This transition enhances the migratory and invasive capabilities of cells by modifying the cell adhesion molecules and ECM components. We investigated the anti-migratory effect of DHTS on TNBC cell lines by studying the Epithelial Mesenchymal Transition (EMT) changes. Conclusion: In this study, we have demonstrated for the first time that DHTS has the potential to inhibit the migration and clonogenicity of highly aggressive TNBC cells by obstructing Epithelial to Mesenchymal Transition

Methods

Results

Conclusion