title: 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.
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.
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. wuning@qdio.ac.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. luojiao2012@163.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. beckyjiang0220@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. wanglijun@qdio.ac.cn.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. 12-12sy@163.com.
authors.forename: Shuaiyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Qingdao Medical University Affiliated Hospital, Qingdao 266070, China. docjack@163.com.
authors.forename: Changhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Qingdao Medical University Affiliated Hospital, Qingdao 266070, China. changqing010336@163.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Fu
authors.affiliation: Qingdao Medical University Affiliated Hospital, Qingdao 266070, China. lijian_19891114@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. shidayong@qdio.ac.cn.
authors.forename: Dayong
authors.initials: D
authors.lastname: Shi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D019012:Integrin beta1 / Q000502:physiology; D008114:Liver Neoplasms, Experimental; D008387:Marine Toxins / Q000737:chemistry / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006842:Hydrocarbons, Brominated; D019012:Integrin beta1; D008387:Marine Toxins; C000605672:bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane; D051417:Focal Adhesion Kinase 1