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Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2013 Oct 01; Vol. 272 (1), pp. 180-90. Date of Electronic Publication: 2013 May 22. - Publication Year :
- 2013
-
Abstract
- 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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Blotting, Western
Cell Line, Tumor
Dependovirus genetics
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Fluorescent Antibody Technique
Humans
Immunohistochemistry
Indicators and Reagents
Matrix Metalloproteinase 7 biosynthesis
Matrix Metalloproteinase 7 physiology
Matrix Metalloproteinase 9 biosynthesis
Matrix Metalloproteinase 9 physiology
Mice
Mice, Hairless
Antineoplastic Agents, Phytogenic
Breast Neoplasms drug therapy
Epithelial-Mesenchymal Transition drug effects
Gene Expression Regulation, Enzymologic drug effects
Matrix Metalloproteinases biosynthesis
Signal Transduction drug effects
Xanthones pharmacology
beta Catenin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 272
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 23707762
- Full Text :
- https://doi.org/10.1016/j.taap.2013.05.011