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Chrysin inhibits metastatic potential of human triple‐negative breast cancer cells by modulating matrix metalloproteinase‐10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway
Author(s) -
Yang Bing,
Huang Jing,
Xiang Tingxiu,
Yin Xuedong,
Luo Xinrong,
Huang Jianbo,
Luo Fuling,
Li Hongyuan,
Li Hongzhong,
Ren Guosheng
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2941
Subject(s) - epithelial–mesenchymal transition , triple negative breast cancer , cancer research , matrix metalloproteinase , pi3k/akt/mtor pathway , protein kinase b , matrix metalloproteinase 9 , signal transduction , breast cancer , chrysin , chemistry , medicine , metastasis , cancer , biochemistry , flavonoid , antioxidant
Chrysin, a naturally occurring flavone, has been shown to inhibit cell proliferation and induce cell apoptosis in various cancers. However, the effect and mechanisms of chrysin on cancer metastasis are still enigmatic. In this study, metastatic triple‐negative breast cancer (TNBC) cell lines were used to evaluate the antimetastatic activity of chrysin. The results showed that chrysin (5, 10 and 20 μM) significantly suppressed TNBC cell migration and invasion in a dose‐dependent manner. Human matrix metalloproteinase (MMP) antibody array demonstrated that MMP‐10 was downregulated by chrysin, which was further verified by Western blotting and ELISA. Moreover, it was shown that chrysin induced increased E‐cadherin expression and decreased expression of vimentin, snail and slug in TNBC cells, suggesting that chrysin had a reversal effect on epithelial–mesenchymal transition. More importantly, it was demonstrated that inhibiting the Akt signal pathway might play a central role in chrysin‐induced antimetastatic activity by regulating MMP‐10 and epithelial–mesenchymal transition. In conclusion, our study indicates that chrysin exerts antimetastatic activities in TNBC cells, which suggests that chrysin might be a potential therapeutic candidate for the treatment of advanced or metastatic breast cancer. Copyright © 2013 John Wiley & Sons, Ltd.