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Int. J. Mol. Sci. 2015, 16(6), 13548-13560; doi:10.3390/ijms160613548

Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects

Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Vassilios Roussis
Received: 14 April 2015 / Revised: 21 May 2015 / Accepted: 29 May 2015 / Published: 12 June 2015
(This article belongs to the Special Issue Bioactivity of Marine Natural Products)
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Abstract

Bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a bromophenol first isolated from Rhodomelaceae confervoides. Our previous studies showed that BDDPM exerts PTP1B-inhibiting activity and anti-cancer activity against a wide range of tumor cells while it also showed lower cytotoxicity against normal cells. In the present study, we found that BDDPM exhibits significant activities toward angiogenesis in vitro. BDDPM inhibits multiple angiogenesis processes, including endothelial cell sprouting, migration, proliferation, and tube formation. Further kinase assays investigations found that BDDPM is a potent selective, but multi-target, receptor tyrosine kinase (RTKs) inhibitor. BDDPM (10 μM) inhibits the activities of fibroblast growth factor receptor 2 and 3 (FGFR2, 3), vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor α (PDGFRα) (inhibition rate: 57.7%, 78.6%, 78.5% and 71.1%, respectively). Moreover, BDDPM also decreases the phosphorylation of protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS), as well as nitric oxide (NO) production in a dose dependent manner. These results indicate that BDDPM can be exploited as an anti-angiogenic drug, or as a lead compound for the development of novel multi-target RTKs inhibitors. View Full-Text
Keywords: bromophenol; anti-angiogenesis; RTKs; multi-target inhibitor; NO; PKB/Akt; eNOS bromophenol; anti-angiogenesis; RTKs; multi-target inhibitor; NO; PKB/Akt; eNOS
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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

Wang, S.; Wang, L.-J.; Jiang, B.; Wu, N.; Li, X.; Liu, S.; Luo, J.; Shi, D. Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects. Int. J. Mol. Sci. 2015, 16, 13548-13560.

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