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Mar. Drugs 2012, 10(9), 2033-2046; doi:10.3390/md10092033
Article

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

1
,
2
,
1
,
1,3
 and
1,3,*
1 Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain 2 Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC-IDIBELL), Barcelona E-08908, Spain 3 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Málaga E-29071, Spain
* Author to whom correspondence should be addressed.
Received: 18 July 2012 / Revised: 3 September 2012 / Accepted: 6 September 2012 / Published: 18 September 2012
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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.
Keywords: aeroplysinin-1; angiogenesis; apoptosis; caspases aeroplysinin-1; angiogenesis; apoptosis; caspases
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Martínez-Poveda, B.; Rodríguez-Nieto, S.; García-Caballero, M.; Medina, M.-Á.; Quesada, A.R. The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway. Mar. Drugs 2012, 10, 2033-2046.

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