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The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells by activating the mitochondrial pathway.

Abstract
Aeroplysinin-1 is a brominated metabolite extracted from the marine sponge Aplysina aerophoba that has been previously characterized by our group as a potent antiangiogenic compound in vitro and in vivo. In this work, we provide evidence of a selective induction of apoptosis by aeroplysinin-1 in endothelial cells. Studies on the nuclear morphology of treated cells revealed that aeroplysinin-1 induces chromatin condensation and nuclear fragmentation, and it increases the percentage of cells with sub-diploid DNA content in endothelial, but not in HCT-116, human colon carcinoma and HT-1080 human fibrosarcoma cells. Treatment of endothelial cells with aeroplysinin-1 induces activation of caspases-2, -3, -8 and -9, as well as the cleavage of apoptotic substrates, such as poly (ADP-ribose) polymerase and lamin-A in a caspase-dependent mechanism. Our data indicate a relevant role of the mitochondria in the apoptogenic activity of this compound. The observation that aeroplysinin-1 prevents the phosphorylation of Bad relates to the mitochondria-mediated induction of apoptosis by this compound.
AuthorsBeatriz Martínez-Poveda, Salvador Rodríguez-Nieto, Melissa García-Caballero, Miguel-Ángel Medina, Ana R Quesada
JournalMarine drugs (Mar Drugs) Vol. 10 Issue 9 Pg. 2033-2046 (Sep 2012) ISSN: 1660-3397 [Electronic] Switzerland
PMID23118719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acetonitriles
  • Angiogenesis Inhibitors
  • BAD protein, human
  • Chromatin
  • Cyclohexenes
  • Lamin Type A
  • bcl-Associated Death Protein
  • aeroplysinin I
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Caspases
Topics
  • Acetonitriles (pharmacology)
  • Angiogenesis Inhibitors (pharmacology)
  • Animals
  • Apoptosis (drug effects)
  • Caspases (metabolism)
  • Cattle
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus (drug effects, metabolism)
  • Chromatin (metabolism)
  • Cyclohexenes (pharmacology)
  • Cytochromes c (drug effects)
  • DNA Fragmentation (drug effects)
  • Endothelial Cells (drug effects, metabolism)
  • HCT116 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lamin Type A (metabolism)
  • Mitochondria (drug effects, metabolism)
  • Phosphorylation (drug effects)
  • Poly(ADP-ribose) Polymerases (metabolism)
  • bcl-Associated Death Protein (metabolism)

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