The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway

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 end...

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Main Authors: Beatriz Martínez-Poveda, Salvador Rodríguez-Nieto, Melissa García-Caballero, Miguel-Ángel Medina, Ana R. Quesada
Format: Article
Language:English
Published: MDPI AG 2012-09-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/10/9/2033
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author Beatriz Martínez-Poveda
Salvador Rodríguez-Nieto
Melissa García-Caballero
Miguel-Ángel Medina
Ana R. Quesada
author_facet Beatriz Martínez-Poveda
Salvador Rodríguez-Nieto
Melissa García-Caballero
Miguel-Ángel Medina
Ana R. Quesada
author_sort Beatriz Martínez-Poveda
collection DOAJ
description 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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spelling doaj.art-299373d564fa42d38b91d9a6b01828882022-12-22T02:18:21ZengMDPI AGMarine Drugs1660-33972012-09-011092033204610.3390/md10092033The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial PathwayBeatriz Martínez-PovedaSalvador Rodríguez-NietoMelissa García-CaballeroMiguel-Ángel MedinaAna R. QuesadaAeroplysinin-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.http://www.mdpi.com/1660-3397/10/9/2033aeroplysinin-1angiogenesisapoptosiscaspases
spellingShingle Beatriz Martínez-Poveda
Salvador Rodríguez-Nieto
Melissa García-Caballero
Miguel-Ángel Medina
Ana R. Quesada
The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
Marine Drugs
aeroplysinin-1
angiogenesis
apoptosis
caspases
title The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
title_full The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
title_fullStr The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
title_full_unstemmed The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
title_short The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
title_sort antiangiogenic compound aeroplysinin 1 induces apoptosis in endothelial cells by activating the mitochondrial pathway
topic aeroplysinin-1
angiogenesis
apoptosis
caspases
url http://www.mdpi.com/1660-3397/10/9/2033
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