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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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Effect of aeroplysinin-1 on endothelial and tumor cell growth. (A) Cell counts of BAEC, HCT-116 and HT1080 grown either in the absence or the presence of 1 µM, 3 µM, 5 µM or 10 µM aeroplysinin-1 (respectively marked as o, ▲, ■, ● and x). Values are means ± SD of quadruplicate samples. (B) Half-maximal inhibitory concentration (IC50) values were calculated from MTT dose-response curves as the concentration of aeroplysinin-1 yielding 50% of control cell survival. They are expressed as means ± SD of three independent experiments with quadruplicate samples each.
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marinedrugs-10-02033-f002: Effect of aeroplysinin-1 on endothelial and tumor cell growth. (A) Cell counts of BAEC, HCT-116 and HT1080 grown either in the absence or the presence of 1 µM, 3 µM, 5 µM or 10 µM aeroplysinin-1 (respectively marked as o, ▲, ■, ● and x). Values are means ± SD of quadruplicate samples. (B) Half-maximal inhibitory concentration (IC50) values were calculated from MTT dose-response curves as the concentration of aeroplysinin-1 yielding 50% of control cell survival. They are expressed as means ± SD of three independent experiments with quadruplicate samples each.

Mentions: The effect of aeroplysinin-1 on endothelial and tumor cell growth was investigated by cell count and by MTT assay. As shown in Figure 2A, aeroplysinin-1 inhibited, in a concentration-dependent manner, the growth of BAEC, HCT-116 and HT-1080, with a complete inhibition of BAEC and HCT-116 cell proliferation, exerted at a concentration of 10 µM. This is in agreement with the antiproliferative effect of aeroplysinin-1 on endothelial cells, previously described by us [5]. Data obtained with the colorimetric MTT assay (Figure 2B) show that aeroplysinin-1 is not a specific inhibitor of endothelial cell growth, as the half-maximal inhibitory concentration (IC50) value of this effect on endothelial cells (BAECs) is in the same range as those obtained with tumor cells (HCT-116 and HT-1080).


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)

Effect of aeroplysinin-1 on endothelial and tumor cell growth. (A) Cell counts of BAEC, HCT-116 and HT1080 grown either in the absence or the presence of 1 µM, 3 µM, 5 µM or 10 µM aeroplysinin-1 (respectively marked as o, ▲, ■, ● and x). Values are means ± SD of quadruplicate samples. (B) Half-maximal inhibitory concentration (IC50) values were calculated from MTT dose-response curves as the concentration of aeroplysinin-1 yielding 50% of control cell survival. They are expressed as means ± SD of three independent experiments with quadruplicate samples each.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

marinedrugs-10-02033-f002: Effect of aeroplysinin-1 on endothelial and tumor cell growth. (A) Cell counts of BAEC, HCT-116 and HT1080 grown either in the absence or the presence of 1 µM, 3 µM, 5 µM or 10 µM aeroplysinin-1 (respectively marked as o, ▲, ■, ● and x). Values are means ± SD of quadruplicate samples. (B) Half-maximal inhibitory concentration (IC50) values were calculated from MTT dose-response curves as the concentration of aeroplysinin-1 yielding 50% of control cell survival. They are expressed as means ± SD of three independent experiments with quadruplicate samples each.
Mentions: The effect of aeroplysinin-1 on endothelial and tumor cell growth was investigated by cell count and by MTT assay. As shown in Figure 2A, aeroplysinin-1 inhibited, in a concentration-dependent manner, the growth of BAEC, HCT-116 and HT-1080, with a complete inhibition of BAEC and HCT-116 cell proliferation, exerted at a concentration of 10 µM. This is in agreement with the antiproliferative effect of aeroplysinin-1 on endothelial cells, previously described by us [5]. Data obtained with the colorimetric MTT assay (Figure 2B) show that aeroplysinin-1 is not a specific inhibitor of endothelial cell growth, as the half-maximal inhibitory concentration (IC50) value of this effect on endothelial cells (BAECs) is in the same range as those obtained with tumor cells (HCT-116 and HT-1080).

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