期刊
MARINE DRUGS
卷 10, 期 9, 页码 2033-2046出版社
MDPI
DOI: 10.3390/md10092033
关键词
aeroplysinin-1; angiogenesis; apoptosis; caspases
资金
- Spanish Ministry of Science and Innovation [PS09/02216, PET2008-0145]
- ISCIII [PS09/02216, PET2008-0145]
- FEDER [PS09/02216, PET2008-0145]
- Andalusian Government [PIE P08-CTS-3759]
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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