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

Marine Drugs

Ning Wu²  Jiao Luo²  Bo Jiang²  Lijun Wang²  Shuaiyu Wang²  Changhui Wang¹  Changqing Fu¹  Jian Li¹  Dayong Shi² 

[1] Qingdao Medical University Affiliated Hospital, Qingdao 266070, China; E-Mails:;Institute of Oceanology,Chinese Academy of Sciences, Qingdao 266071, China; E-Mails:

关键词: bis (2;    3-dibromo-4;    5-dihydroxy-phenyl)-methane (BDDPM);    anti-metastatic activity;    cell adhesion;    β1-integrin;    FAK;    BEL-7402 cell;   

DOI  :  10.3390/md13021010

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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