Antiangiogenic activity of aeroplysinin-1, a brominated compound isolated from a marine sponge.
(+)-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.
Rodríguez-Nieto
Salvador
S
Departamento de Biología Molecular y Bioquímica, Universidad de Málaga, Campus de Teatinos, 29071-Málaga, Spain.
González-Iriarte
Mauricio
M
Carmona
Rita
R
Muñoz-Chápuli
Ramón
R
Medina
Miguel Angel
MA
Quesada
Ana R
AR
D000097:Acetonitriles / Q000494:pharmacology*; D000482:Allantois / Q000098:blood supply / Q000166:cytology / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000166:cytology / Q000187:drug effects; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011161:Porifera / Q000737:chemistry*
D000097:Acetonitriles; D053138:Cyclohexenes; C042151:aeroplysinin I; D020778:Matrix Metalloproteinase 2