Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and ¦Â-catenin signaling pathway
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- 作者：Hongzhong Li ; Jing Huang ; Bing Yang ; Tingxiu Xiang ; Xuedong Yin ; Weiyan Peng ; Wei Cheng ; Jingyuan Wan ; Fuling Luo ; Hongyuan Li ; Guosheng Ren
- 关键词：MMP ; matrix metalloproteinase ; EMT ; epithelial&ndash ; mesenchymal transition ; MET ; mesenchymal&ndash ; epithelial transition ; ER ; estrogen receptor ; GSK-3¦Â ; glycogen synthase kinase 3¦Â ; DMSO ; dimethyl sulfoxide ; PI ; propidium iodide ; IHC ; immunohistochemis
- 刊名：Toxicology and Applied Pharmacology
- 出版年：2013
- 出版时间：1 October, 2013
- 年：2013
- 卷：272
- 期：1
- 页码：180-190
- 全文大小：2804 K
文摘
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 ¦Â-catenin pathway. Subsequent experiments showed that inhibiting ¦Â-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 ¦Â-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.