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Antiangiogenic activity of aeroplysinin‐1, a brominated compound isolated from a marine sponge
Author(s) -
Rodríguez-Nieto Salvador,
González-Iriarte Mauricio,
Carmona Rita,
Muñoz-Chápuli Ramón,
Medina Miguel Angel,
Quesada Ana R.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0427fje
Subject(s) - angiogenesis , matrigel , in vivo , sponge , endothelial stem cell , chorioallantoic membrane , chemistry , matrix metalloproteinase , in vitro , apoptosis , endothelium , cell culture , microbiology and biotechnology , biochemistry , biology , pharmacology , cancer research , endocrinology , botany , genetics
(+)‐Aeroplysinin‐1, an antibacterial brominated compound produced by certain sponges, was selected during a blind high‐throughput screening for new potential antiangiogenic compounds obtained from marine organisms. In a variety of experimental systems, representing the sequential events of the angiogenic process, aeroplysinin‐1 treatment of endothelial cells resulted in strong inhibitory effects. Aeroplysinin‐1 inhibited the growth of endothelial cells in culture and induced endothelial cell apoptosis. Capillary tube formation on Matrigel was completely abrogated by addition of aeroplysinin‐1 at the low micromolar range. Aeroplysinin‐1 also exhibited a clear inhibitory effect on the migration capabilities of endothelial cells. Zymographic assays showed that aeroplysinin‐1 treatment produced a decrease in the concentration of matrix metalloproteinase‐2 and urokinase in conditioned medium from endothelial cells. Finally, aeroplysinin‐1 exhibited a dose‐dependent inhibitory effect on the in vivo chorioallantoic membrane assay, showing potent apoptosis‐inducing activity in the developing endothelium. The in vivo inhibition of angiogenesis by aeroplysinin‐1 was confirmed by the Matrigel plug assay. Together, our data indicate that aeroplysinin‐1 is a compound that interferes with key events in angiogenesis, making it a promising drug for further evaluation in the treatment of angiogenesis‐related pathologies.