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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MDPI AG
2012-09-01
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Series: | Marine Drugs |
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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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issn | 1660-3397 |
language | English |
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publishDate | 2012-09-01 |
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series | Marine Drugs |
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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