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en Gene Expression Changes in Pomegranate Peel Extract-Treated Triple-Negative Breast Cancer Cells زیست شناسی سلولی Cell Biology مقالات اصلی Original Article <div style="text-align: justify;"><strong><em>Background:</em></strong> 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.</div> <div style="text-align: justify;"><strong><em>Methods:</em></strong> 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.     </div> <div style="text-align: justify;"><strong><em>Results:</em></strong> 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.</div> <div style="text-align: justify;"><strong><em>Conclusions:</em></strong> Transcriptional changes in ICAM-1, MMP9, fibronectin, and VEGF may contribute to PPE-mediated antimetastatic effects in TNBC.</div> Gene Expression, Metastasis, Natural Product, Pomegranate Peel Extract (PPE), Triple Negative Breast Cancer. 102 109 http://rbmb.net/browse.php?a_code=A-10-149-1&slc_lang=en&sid=1 Naghmeh Ahmadiankia Ahmadian@shmu.ac.ir 10031947532846006401 10031947532846006401 No Cancer Prevention Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. & School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Mehdi Bagheri 10031947532846006402 10031947532846006402 Yes Imam Hossein Center for Education, Research and Treatment, Shahroud University of Medical Sciences, Shahroud, Iran. Mozhgan Fazli 10031947532846006403 10031947532846006403 No School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.