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

Marine Drugs

Beatriz Martínez-Poveda²  Salvador Rodríguez-Nieto¹  Melissa Garc໚-Caballero²  Miguel-Ángel Medina² 

[1] Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC-IDIBELL), Barcelona E-08908, Spain;Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain;

关键词: aeroplysinin-1;    angiogenesis;    apoptosis;    caspases;   

DOI  :  10.3390/md10092033

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.