title: The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells by activating the mitochondrial pathway.
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.
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Poveda
authors.affiliation: Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC-IDIBELL), Barcelona E-08908, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Rodríguez-Nieto
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain.
authors.forename: Melissa
authors.initials: M
authors.lastname: García-Caballero
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Málaga E-29071, Spain.
authors.forename: Miguel-Ángel
authors.identifier: 0000-0001-7275-6462
authors.initials: MÁ
authors.lastname: Medina
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Málaga E-29071, Spain.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Quesada
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D053138:Cyclohexenes / Q000494:pharmacology*; D045304:Cytochromes c / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000097:Acetonitriles; D020533:Angiogenesis Inhibitors; C494819:BAD protein, human; D002843:Chromatin; D053138:Cyclohexenes; D034904:Lamin Type A; D051025:bcl-Associated Death Protein; C042151:aeroplysinin I; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: aeroplysinin-1; angiogenesis; apoptosis; caspases