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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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(A) Chemical structure of aeroplysinin-1; (B) Summary of its anti-angiogenic properties.
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marinedrugs-10-02033-f001: (A) Chemical structure of aeroplysinin-1; (B) Summary of its anti-angiogenic properties.

Mentions: Aeroplysinin-1 is a naturally occurring brominated tyrosine metabolite extracted from the marine sponge Aplisina aerophoba, where it seems to play a defensive role [4] (Figure 1A). In the course of a blind high-throughput screening for new potential inhibitors of angiogenesis obtained from marine organisms, our group selected aeroplysinin-1 and characterized it as a potent antiangiogenic compound in vitro and in vivo [5]. Aeroplysinin-1 was shown to inhibit angiogenesis in the chick chorioallantoic membrane and in subcutaneous Matrigel implants in mice, and to interfere with key steps of angiogenesis in endothelial cells, including proliferation, migration, capillary tube formation and the ability to invade and remodel the extracellular matrix. In a previous work, we demonstrated that aeroplysinin-1 could induce apoptosis in endothelial cells, although the mechanisms leading to apoptosis remained elusive (Figure 1B).


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)

(A) Chemical structure of aeroplysinin-1; (B) Summary of its anti-angiogenic properties.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

marinedrugs-10-02033-f001: (A) Chemical structure of aeroplysinin-1; (B) Summary of its anti-angiogenic properties.
Mentions: Aeroplysinin-1 is a naturally occurring brominated tyrosine metabolite extracted from the marine sponge Aplisina aerophoba, where it seems to play a defensive role [4] (Figure 1A). In the course of a blind high-throughput screening for new potential inhibitors of angiogenesis obtained from marine organisms, our group selected aeroplysinin-1 and characterized it as a potent antiangiogenic compound in vitro and in vivo [5]. Aeroplysinin-1 was shown to inhibit angiogenesis in the chick chorioallantoic membrane and in subcutaneous Matrigel implants in mice, and to interfere with key steps of angiogenesis in endothelial cells, including proliferation, migration, capillary tube formation and the ability to invade and remodel the extracellular matrix. In a previous work, we demonstrated that aeroplysinin-1 could induce apoptosis in endothelial cells, although the mechanisms leading to apoptosis remained elusive (Figure 1B).

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