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The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells by activating the mitochondrial pathway.

Martínez-Poveda B, Rodríguez-Nieto S, García-Caballero M, Medina MÁ, Quesada AR - Mar Drugs (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain. bmpoveda@gmail.com

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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Effects of aeroplysinin-1 on Bad phosphorylation in human umbilical vein endothelial cells (HUVEC) and human HCT-116 colon carcinoma cells. Negative control (C−) corresponds to starved but not induced cells; positive control (C+) corresponds to starved and serum-induced cells. Identical results were obtained in two independent experiments.
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marinedrugs-10-02033-f006: Effects of aeroplysinin-1 on Bad phosphorylation in human umbilical vein endothelial cells (HUVEC) and human HCT-116 colon carcinoma cells. Negative control (C−) corresponds to starved but not induced cells; positive control (C+) corresponds to starved and serum-induced cells. Identical results were obtained in two independent experiments.

Mentions: The BH3-only pro-apoptotic protein Bad is regulated by phosphorylation-dephosphorylation in response to extracellular stimuli. The phosphorylation status of Bad determines its pro-apoptotic activity at the mitochondrial level [15], facilitating its depolarization by interacting and restraining the anti-apoptotic protein Bcl-XL. Therefore, we decided to study the effect of aeroplysinin-1 on the phosphorylation status of Bad in endothelial cells by serum deprivation and re-stimulation, with or without addition of aeroplysinin-1. As shown in Figure 6, aeroplysinin-1 prevented phosphorylation of Bad in HUVE cells in a dose-dependent manner, but not in HCT-116 cells, reinforcing the previously shown data regarding the endothelial selectivity of aeroplysinin-1 apoptogenic activity (Figure 3 and Figure 6).


The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells by activating the mitochondrial pathway.

Martínez-Poveda B, Rodríguez-Nieto S, García-Caballero M, Medina MÁ, Quesada AR - Mar Drugs (2012)

Effects of aeroplysinin-1 on Bad phosphorylation in human umbilical vein endothelial cells (HUVEC) and human HCT-116 colon carcinoma cells. Negative control (C−) corresponds to starved but not induced cells; positive control (C+) corresponds to starved and serum-induced cells. Identical results were obtained in two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475271&req=5

marinedrugs-10-02033-f006: Effects of aeroplysinin-1 on Bad phosphorylation in human umbilical vein endothelial cells (HUVEC) and human HCT-116 colon carcinoma cells. Negative control (C−) corresponds to starved but not induced cells; positive control (C+) corresponds to starved and serum-induced cells. Identical results were obtained in two independent experiments.
Mentions: The BH3-only pro-apoptotic protein Bad is regulated by phosphorylation-dephosphorylation in response to extracellular stimuli. The phosphorylation status of Bad determines its pro-apoptotic activity at the mitochondrial level [15], facilitating its depolarization by interacting and restraining the anti-apoptotic protein Bcl-XL. Therefore, we decided to study the effect of aeroplysinin-1 on the phosphorylation status of Bad in endothelial cells by serum deprivation and re-stimulation, with or without addition of aeroplysinin-1. As shown in Figure 6, aeroplysinin-1 prevented phosphorylation of Bad in HUVE cells in a dose-dependent manner, but not in HCT-116 cells, reinforcing the previously shown data regarding the endothelial selectivity of aeroplysinin-1 apoptogenic activity (Figure 3 and Figure 6).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Málaga E-29071, Spain. bmpoveda@gmail.com

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.

Show MeSH
Related in: MedlinePlus