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.
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Authors | Beatriz Martínez-Poveda, Salvador Rodríguez-Nieto, Melissa García-Caballero, Miguel-Ángel Medina, Ana R Quesada |
Journal | Marine drugs
(Mar Drugs)
Vol. 10
Issue 9
Pg. 2033-2046
(Sep 2012)
ISSN: 1660-3397 [Electronic] Switzerland |
PMID | 23118719
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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