Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;124(12):1900-1918.
doi: 10.1002/jcb.30496. Epub 2023 Nov 22.

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

Venkataswamy Mallepogu  1 , Karunakaran Reddy Sankaran  1 , Chiranjeevi Pasala  2 , Lokesh Reddy Bandi  3 , Rajasekhar Maram  3 , Uma Maheswari Amineni  2 , Balaji Meriga  1
Affiliations

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

Venkataswamy Mallepogu et al. J Cell Biochem. 2023 Dec.

Abstract

Epithelial-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.

Keywords: EMT markers; apoptosis; breast cancer; cell viability; docking; ursolic acid.

PubMed Disclaimer

References

REFERENCES

    1. DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin. 2011;61(6):408-418. doi:10.3322/caac.20134
    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
    1. Sun YS, Zhao Z, Yang ZN, et al. Risk factors and preventions of breast cancer. Int J Biol Sci. 2017;13(11):1387-1397. doi:10.7150/ijbs.21635
    1. Sahayarayan JJ, Rajan KS, Vidhyavathi R, et al. In-silico protein-ligand docking studies against the estrogen protein of breast cancer using pharmacophore based virtual screening approaches. Saudi J Biol Sci. 2021;28(1):400-407. doi:10.1016/j.sjbs.2020.10.023
    1. Sathishkumar K, Chaturvedi M, Das P, Stephen S, Mathur P. Cancer incidence estimates for 2022 & projection for 2025: result from National Cancer Registry Programme, India. Indian J Med Res. 2022;156(4&5):598-607. doi:10.4103/ijmr.ijmr_1821_22

Publication types

LinkOut - more resources