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

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

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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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) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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