The Antiangiogenic Compound Aeroplysinin-1 Induces Apoptosis in Endothelial Cells by Activating the Mitochondrial Pathway |
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Authors: | Beatriz Mart??nez-Poveda Salvador Rodr??guez-Nieto Melissa Garc??a-Caballero Miguel-??ngel Medina Ana R Quesada |
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Institution: | 1.Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain; Email: (B.M.-P.); (M.G.-C.); (M.-A.M.);2.Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC-IDIBELL), Barcelona E-08908, Spain; Email: ;3.Centre for Biomedical Network Research on Rare Diseases (CIBERER), Málaga E-29071, Spain |
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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. |
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Keywords: | aeroplysinin-1 angiogenesis apoptosis caspases |
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