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Embelin Inhibits Invasion and Migration of MDA‐MB‐231 Breast Cancer Cells by Suppression of CXC Chemokine Receptor 4, Matrix Metalloproteinases‐9/2, and Epithelial–Mesenchymal Transition
Author(s) -
Lee Hanwool,
Ko JeongHyeon,
Baek Seung Ho,
Nam Dongwoo,
Lee Seok Geun,
Lee Junhee,
Yang Woong Mo,
Um JaeYoung,
Kim SungHoon,
Shim Bum Sang,
Ahn Kwang Seok
Publication year - 2016
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5612
Subject(s) - epithelial–mesenchymal transition , downregulation and upregulation , cancer research , metastasis , chemokine receptor , cxc chemokine receptors , cxcr4 , vimentin , twist transcription factor , cancer cell , matrix metalloproteinase , cell migration , biology , cxcl14 , chemokine , chemistry , microbiology and biotechnology , receptor , medicine , cancer , immunology , cell , immunohistochemistry , biochemistry , gene
Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant. Recent scientific evidence shows that EB induces apoptosis and inhibits migration and invasion in highly metastatic human breast cancer cells. However, the exact mechanisms of EB in tumor metastasis and invasion have not been fully elucidated. Here, we investigated the underlying mechanisms of antimetastatic activities of EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4) as well as matrix metalloproteinase (MMP)‐9/2 expression and upregulated the tissue inhibitor of metalloproteinase 1 expression in MDA‐MB‐231 cells under noncytotoxic concentrations but not in MCF‐7 cells. Additionally, EB inhibited the CXC motif chemokine ligand 12 induced invasion and migration activities of MDA‐MB‐231 cells. A detailed study of underlying mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by the downregulation of mRNA expression and suppression of nuclear factor‐kappa B (NF‐κB) activation. It further reduced the binding of NF‐κB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker proteins (neural cadherin and vimentin) and concurrently upregulated epithelial markers (epithelial cadherin and occludin). Overall, these findings suggest that EB can abrogate breast cancer cell invasion and metastasis by suppression of CXCR4, MMP‐9/2 expressions, and inhibition of epithelial–mesenchymal transition and thus may have a great potential to suppress metastasis of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.