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

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.

Keywords

Apoptosis / Breast cancer / Deep sequencing / Epithelial-to-mesenchymal transition / Estrogen receptor / Transcriptomics

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