title: Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway.
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.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.forename: Xuedong
authors.initials: X
authors.lastname: Yin
authors.forename: Weiyan
authors.initials: W
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.forename: Fuling
authors.initials: F
authors.lastname: Luo
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D051379:Mice; D008812:Mice, Hairless; D015398:Signal Transduction / Q000187:drug effects*; D044004:Xanthones / Q000494:pharmacology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D044004:Xanthones; D051176:beta Catenin; C013592:mangiferin; D020782:Matrix Metalloproteinases; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9
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