Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA‐MB‐231 and MCF‐7 breast cancer cells, an in‐vitro and in silico studies

Author:

Mallepogu Venkataswamy1,Sankaran Karunakaran Reddy1,Pasala Chiranjeevi2,Bandi Lokesh Reddy3,Maram Rajasekhar3,Amineni Uma Maheswari2,Meriga Balaji1ORCID

Affiliation:

1. Department of Biochemistry Sri Venkateswara University Tirupati Andhra Pradesh India

2. Department of Bioinformatics Sri Venkateswara Institute of Medical Sciences Tirupati Andhra Pradesh India

3. Department of Zoology Sri Venkateswara University Tirupati Andhra Pradesh India

Abstract

AbstractEpithelial–mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA‐MB‐231 and MCF‐7 breast cancer cells. The apparent anticancer activity of UA on MDA‐MB‐231 and MCF‐7 cells was evident from IC50 values of 14.98 and 15.99 μg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA‐MB‐231 and MCF‐7 cells were treated with 20 μg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G0/G1 phase, S phase, G2/M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum‐polarized‐ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with −53.865, −48.971 and −40.617 MMGBSA (ΔGbind) scores, respectively. The long‐range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent.

Publisher

Wiley

Subject

Cell Biology,Molecular Biology,Biochemistry

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