Pomegranate peel extract inhibits expression of β-catenin, epithelial mesenchymal transition, and metastasis in triple negative breast cancer cells

Abstract

The standard treatment for triple-negative breast cancer (TNBC) is chemotherapy, which is highly toxic to patients; thereby, there is a need to identify safer and more effective therapeutic approaches. Medicinal plants constitute a common alternative for cancer treatment. Pomegranate is a well-known fruit in this context, but its antimetastatic property has not been extensively studied. As breast cancer-related deaths from TNBC are mainly due to metastasis, the present study was designed to investigate the antimigratory effect of pomegranate peel extract (PPE) on TNBC cells. For this purpose, the MDA-MB-231 cells were treated with different concentrations of PPE for 24, 48 and 72 hr. The effects of PPE on cell migration and invasion were determined by wound healing and transwell assays. To address the possible molecular mechanisms underlying the antimetastatic effect of PPE, real-time quantitative PCR analysis of selected epithelial mesenchymal transition (EMT) markers were performed. Moreover, the expression of β-catenin as a critical factor in promoting cancer metastasis was examined. PPE markedly inhibited the migration and invasion of cells at concentrations of 25, 50, 100, 250, 500, and 1000µg/ml. At relatively high concentrations (500, 1000µg/ml), PPE induced apoptosis. Moreover, PPE decreased the gene expression of vimentin, ZEB1, and β-catenin and also increased the expression of E-cadherin in TNBC cells. The protein level of β-catenin, as measured using western analysis, revealed a time-dependent decrease at the concentration of 1000µg/ml PPE. Downregulation of EMT markers and β-catenin showed accordance with the inhibition of migration and invasion. The present data show that PPE could be a promising drug candidate to reduce metastasis in TNBC cells.