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.
Highlights
Bromophenol compounds are frequently isolated from various marine red algae and have been reported to exhibit a wide spectrum of pharmacological activities including antibacterial, antimicrobial, and antitumor activities [1,2,3,4]
The results showed that the BEL-7402 cells without treatment had the typical characters of human liver cancer cells, most of which were spindle-shaped with smooth edges and firmly attached to the surfaces of the cell culture dish (Figure 2A)
BEL-7402 cell adhesion to poly-L-lysine (p > 0.05), a non-extracellular matrix (ECM) matrix. These results demonstrate that the treatment of BEL-7402 cells with BDDPM could inhibit the ability of these cells to adhere to ECM
Summary
Bromophenol compounds are frequently isolated from various marine red algae and have been reported to exhibit a wide spectrum of pharmacological activities including antibacterial, antimicrobial, and antitumor activities [1,2,3,4]. The Leathesia nana extract containing large amounts of bromophenol derivatives inhibited the growth of Sarcoma 180 tumors in mice [7]. Accumulated evidence, both in vitro and in vivo, indicates that marine bromophenols may be a promising group of anticancer compounds. FAK-associated cell signaling plays an important role in cell motility and invasion. MTT assay was performed to determine the growth inhibition of different cancer cells and HUVEC cells by BDDPM.
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