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Mar. Drugs 2015, 13(2), 1010-1025; doi:10.3390/md13021010

Marine Bromophenol Bis (2,3-Dibromo-4,5-dihydroxy-phenyl)-methane Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Modulating β1-Integrin/FAK Signaling

1
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
2
Qingdao Medical University Affiliated Hospital, Qingdao 266070, China
*
Author to whom correspondence should be addressed.
Academic Editor: Sergey A. Dyshlovoy
Received: 31 December 2014 / Revised: 30 January 2015 / Accepted: 2 February 2015 / Published: 13 February 2015
(This article belongs to the Collection Marine Compounds and Cancer)
View Full-Text   |   Download PDF [996 KB, uploaded 24 February 2015]   |  

Abstract

Bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL). Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM). Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL) significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL) completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9) is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK) is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents. View Full-Text
Keywords: bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM); anti-metastatic activity; cell adhesion; β1-integrin; FAK; BEL-7402 cell bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM); anti-metastatic activity; cell adhesion; β1-integrin; FAK; BEL-7402 cell
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wu, N.; Luo, J.; Jiang, B.; Wang, L.; Wang, S.; Wang, C.; Fu, C.; Li, J.; Shi, D. Marine Bromophenol Bis (2,3-Dibromo-4,5-dihydroxy-phenyl)-methane Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Modulating β1-Integrin/FAK Signaling. Mar. Drugs 2015, 13, 1010-1025.

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