Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial-mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer.
Keywords: Breast cancer; DMSO; ECM; EMT; ER; Epithelial–mesenchymal transition; GSK-3β; IHC; MET; MMP; Mangiferin; Matrix metalloproteinase; PI; SD; SP; dimethyl sulfoxide; epithelial–mesenchymal transition; estrogen receptor; extracellular matrix; glycogen synthase kinase 3β; immunohistochemistry; matrix metalloproteinase; mesenchymal–epithelial transition; propidium iodide; standard deviation; streptavidin-peroxidase; β-Catenin.
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