Serveur d'exploration Chloroquine

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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

Identifieur interne : 000E18 ( Main/Exploration ); précédent : 000E17; suivant : 000E19

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

Auteurs : Hanwool Lee [Corée du Sud] ; Jeong-Hyeon Ko [Corée du Sud] ; Seung Ho Baek [Corée du Sud] ; Dongwoo Nam [Corée du Sud] ; Seok Geun Lee [Corée du Sud] ; Junhee Lee [Corée du Sud] ; Woong Mo Yang [Corée du Sud] ; Jae-Young Um [Corée du Sud] ; Sung-Hoon Kim [Corée du Sud] ; Bum Sang Shim [Corée du Sud] ; Kwang Seok Ahn [Corée du Sud]

Source :

RBID : ISTEX:0DEE67EBFC190620F5F6DF24DDF6DAA58D7DD1F6

Abstract

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.

Url:
DOI: 10.1002/ptr.5612


Affiliations:


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<div type="abstract">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.</div>
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