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ORIGINAL RESEARCH ARTICLE

Ellagic acid from Terminalia leiocarpa downregulates estrogen-dependent signaling and epithelial-to-mesenchymal transition canonical pathways in MCF-7 cells

Temitope O. Lawal1 ,  Pinal N. Kanabar2 ,  Nina S. Los3 ,  Shitalben M. Patel1 ,  Mark Maienschein-Cline2 ,  Zarema H. Arbieva3 ,  Bolanle A. Adeniyi1 ,  Gail B. Mahady1*
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1 Department of Pharmacy Practice, Retzky College of Pharmacy, World Health Organization Collaborating Centre for Traditional Medicine, University of Illinois Chicago, Chicago, Illinois, United States of America
2 Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, Illinois, United States of America
3 Genomics Research Core, Research Resources Center, University of Illinois Chicago, Chicago, Illinois, United States of America
IMO, 025470062 https://doi.org/10.36922/IMO025470062
Received: 19 November 2025 | Revised: 14 January 2026 | Accepted: 21 January 2026 | Published online: 7 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Breast cancer remains the most diagnosed cancer among women worldwide, and its prevalence continues to increase annually. Previously, we reported that ellagic acid (EA), a compound isolated from Terminalia leiocarpa (DC.) Baill., a plant used in Nigerian traditional medicine, inhibited the proliferation of cultured human MCF-7 breast cancer cells. EA is a pharmacologically active polyphenolic compound with antioxidant, anti-inflammatory, and anti-estrogenic activities. In this work, we investigated the effects of EA on the transcriptome of MCF-7 cells using next-generation sequencing. After EA treatment, MCF-7 cells were harvested, and total RNA was isolated and used to prepare RNA sequencing libraries. Sequencing was performed using NovaSeq 6000. The results showed that EA significantly altered gene expression patterns in MCF-7 cells. Bioinformatic analysis of the sequencing data revealed that 4,848 transcripts were differentially expressed, with 2,180 upregulated genes and 2,668 downregulated genes (q ≤ 0.01). Ingenuity Pathway Analysis indicated that EA-induced expression changes mapped to 98 canonical pathways, including upregulation of apoptosis signaling pathways and downregulation of estrogen signaling and estrogen-dependent breast cancer signaling pathways (q ≤ 0.05). Furthermore, EA downregulated gene expression in the epithelial-to-mesenchymal transition (EMT) canonical pathway, such as PRRX1/2, TGF, TWIST1, and VIM. These data indicate that EA has multiple mechanisms of action in MCF-7 cells, including the induction of apoptosis and the reduction of both estrogen and EMT signaling. Thus, with further research, EA may serve as an inexpensive, safe, and effective treatment for breast cancer and metastatic diseases.

Graphical abstract
Keywords
Apoptosis
Breast cancer
Deep sequencing
Epithelial-to-mesenchymal transition
Estrogen receptor
Transcriptomics
Funding
This work was funded by a Schlumberger Faculty of the Future Foundation Fellowship award to TOL. PK and MMC were supported partly by the University of Illinois at Chicago (UIC) Center for Clinical and Translational Science (CCTS) under Grant #UL1TR002003 from the National Center for Advancing Translational Sciences, National Institutes of Health. The funding agency had no role in the design of the study, the collection, analysis, or interpretation of data, or the writing of the manuscript.
Conflict of interest
The authors declare that they have no competing interests.
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Innovative Medicines & Omics, Electronic ISSN: 3060-8740 Print ISSN: 3060-8910, Published by AccScience Publishing
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