title: 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.
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.
authors.affiliation: Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hanwool
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Ko
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Baek
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Nam
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Seok Geun
authors.initials: SG
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Junhee
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Woong Mo
authors.initials: WM
authors.lastname: Yang
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Um
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Bum Sang
authors.initials: BS
authors.lastname: Shim
authors.affiliation: College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D016227:Benzoquinones / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D016227:Benzoquinones; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; C010945:embelin
keywords: CXCR4; EMT; MMP; breast cancer; embelin