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The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain
Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC-IDIBELL), Barcelona E-08908, Spain
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Málaga E-29071, Spain
* Author to whom correspondence should be addressed.
Received: 18 July 2012; in revised form: 3 September 2012 / Accepted: 6 September 2012 / Published: 18 September 2012
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
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MDPI and ACS Style
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.
Martínez-Poveda B, Rodríguez-Nieto S, García-Caballero M, Medina M-Á, Quesada AR. The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway. Marine Drugs. 2012; 10(9):2033-2046.
Martínez-Poveda, Beatriz; Rodríguez-Nieto, Salvador; García-Caballero, Melissa; Medina, Miguel-Ángel; Quesada, Ana R. 2012. "The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway." Mar. Drugs 10, no. 9: 2033-2046.