Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

• Mangiferin inhibits growth and metastatic potential in breast cancer cells.
• Mangiferin down-regulates MMP-7 and -9 in breast cancer cells.
• Mangiferin induces the reversal of EMT in metastatic breast cancer cells.
• Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells.
• Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

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.