Gene Expression Changes in Pomegranate Peel Extract-Treated Triple-Negative Breast Cancer Cells

摘要

Background: Triple-negative breast cancer (TNBC) is treated with highly aggressive non-targeted chemotherapies. Safer and more effective therapeutic approaches than those currently in use are needed. Natural pomegranate peel extract (PPE) has recently been found to inhibit breast cancer progression; however, its mechanisms of action remain unclear. We hypothesized that transcriptional changes in the genes encoding the adherence proteins of intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF), may explain, at least in part, the anti-metastatic properties of PPE. Recently, the tumor microenvironment has been recognized as a key contributor to cancer progression. We speculated that PPE acts by modulating matrix glycoproteins including MMP9 and fibronectin. Moreover, we hypothesized that VEGF, which is required for tumor development, may contribute to the antimetastatic effects of PPE. Methods: To address these possibilities, MDA-MB-231 cells were treated with different doses of PPE at different time points. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. Cell migration was detected with a transwell assay. Gene expression changes were analyzed by real-time PCR. Results: Exposure to PPE resulted in TNBC cell death and markedly inhibited PPE-resistant cell migration. Moreover, PPE up-regulated the expression of ICAM-1, a protein essential for cell adhesion, and down-regulated the expression of MMP9, fibronectin, and VEGF, the products of which contribute to cancer cell migration. Conclusions: Transcriptional changes in ICAM-1, MMP9, fibronectin, and VEGF may contribute to PPE-mediated antimetastatic effects in TNBC.