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Glabridin inhibits cancer stem cell‐like properties of human breast cancer cells: An epigenetic regulation of miR‐148a/SMAd2 signaling
Author(s) -
Jiang Fei,
Li Yuan,
Mu Juan,
Hu Chunyan,
Zhou Ming,
Wang Xingxing,
Si Lu,
Ning Shilong,
Li Zhong
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22333
Subject(s) - cancer stem cell , biology , cancer research , cancer cell , cancer , breast cancer , metastasis , microrna , stem cell , mesenchymal stem cell , stromal cell , microbiology and biotechnology , biochemistry , genetics , gene
In breast cancer, the cancer stem cells (CSCs) are thought to be the main cause of metastasis and recurrence. Targeting of CSCs or cancer cells with stem cell‐like properties has become a new approach for the treatment of breast cancer. Glabridin (GLA), a phytochemical from the root of Glycyrrhiza glabra , exhibited effective antitumor properties in various human cancer cells. However, the roles of GLA in the regulation of CSC‐like properties and the underlying molecular mechanisms remain unclear. Here, we reported that GLA attenuated the CSC‐like properties through microRNA‐148a (miR‐148a)/transforming growth factor beta (TGFβ)‐SMAD2 signal pathway in vitro and in vivo . In MDA‐MB‐231 and Hs‐578T breast cancer cell lines, GLA enhanced the expression of miR‐148a through DNA demethylation. By targeting of the SMAD2 ‐3′‐UTR, miR‐148a blocked the expression/activation of SMAD2, and in turn, restored the epithelial characteristics, adhesive abilities, and CSC‐like properties. Furthermore, in mouse xenograft models, we also confirmed that GLA attenuated the tumor growth, mesenchymal characteristics, and CSCs‐like properties via demethylation‐activated miR‐148a. Our findings suggested a potential treatment strategy to reduce the CSCs‐like properties, and therefore enhance the effectiveness of breast cancer therapy. © 2015 Wiley Periodicals, Inc.