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 Feb 13;13(2):1010-25. doi: 10.3390/md13021010.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • Hydrocarbons, Brominated / pharmacology*
  • Integrin beta1 / physiology
  • Liver Neoplasms, Experimental
  • Marine Toxins / chemistry
  • Marine Toxins / pharmacology*
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Metastasis / prevention & control

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Hydrocarbons, Brominated
  • Integrin beta1
  • Marine Toxins
  • bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane
  • Focal Adhesion Kinase 1