IB05204, a dichloropyridodithienotriazine, inhibits angiogenesis <i>in vitro</i> and <i>in vivo</i>

Martínez‐Poveda, Beatriz; Muñoz‐Chápuli, Ramón; Rodriguez-Nieto, Salvador; Quintela, José M.; Fernández, Antonio; Medina, Miguel Ángel; Quesada, Ana R.

doi:10.1158/1535-7163.mct-07-0136

Cited by 19 publications

(16 citation statements)

References 45 publications

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“…Apoptosis assays were carried out, after 24 h of incubation in the presence of kahweol, by staining of nuclei with Hoechst as described by us elsewhere [14].…”

Section: Methodsmentioning

confidence: 99%

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Anti-Angiogenic and Anti-Inflammatory Properties of Kahweol, a Coffee Diterpene

2011

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BackgroundEpidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules.Methodology/Principal FindingsThe experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish), the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells.Conclusion/SignificanceTaken together, our data indicate that, indeed, kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers.

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“…Apoptosis assays were carried out, after 24 h of incubation in the presence of kahweol, by staining of nuclei with Hoechst as described by us elsewhere [14].…”

Section: Methodsmentioning

confidence: 99%

“…Our group is actively involved in the search for new modulators of angiogenesis from natural sources [10], [11], [12], [13], [14]. In the present study, the effects of kahweol on two in vivo and one ex vivo model of angiogenesis and on several key steps of the process are described.…”

Section: Introductionmentioning

confidence: 93%

Anti-Angiogenic and Anti-Inflammatory Properties of Kahweol, a Coffee Diterpene

2011

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“…Likewise, it has been previously reported that a number of endogenous and exogenous angiogenesis inhibitors induce endothelial cell apoptosis, including thrombospondin-1 [6], pigment epithelium-derived factor [7], adiponectin [8], neovastat [9] and IB05204 [10], among many others. It has been suggested that endothelial cell apoptosis induced by a variety of mechanisms might be responsible for their angiogenesis-inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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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“…It has been suggested that endothelial cell apoptosis, induced by a variety of mechanisms, might be responsible for the angiogenesis-inhibitory activity of a number of endogenous and exogenous angiogenesis inhibitors including thrombospondin-1, pigment epithelium-derived factor, adiponectin, neovastat, and IB05204, among many others [159][160][161][162]. During apoptosis, extrinsic or intrinsic signals activate caspases, which in turn induce DNA fragmentation, DNA budding, and the chromatin condensation characteristic of programmed cell death (reviewed in [163]).…”

Section: Compounds That Inhibit One or Several Specific Functions Of mentioning

confidence: 99%

Marine Sponge Derived Antiangiogenic Compounds

Quesada

Martínez‐Poveda

Rodriguez-Nieto³

et al. 2014

Handbook of Anticancer Drugs From Marine Origin

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Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number of antiangiogenic strategies being tested in preclinical and clinical trials. Nowadays the clinical development of antiangiogenic therapies seems to be unstoppable, not only for cancer, but also for an increasing number of non-neoplasic angiogenesis-related diseases. Although most of the natural compounds previously described as inhibitors of angiogenesis have been isolated from plants and terrestrial microorganisms, increasing attention is being paid to the development of marine-derived antiangiogenic agents. Marine organisms produce interesting and singular pharmacological lead compounds, derived from the large diversity of marine habitats and environmental conditions. Among the many different types of marine organisms used as a source for drug discovery, sponges represent one of the most promising sources of leads in the research of new cancer drugs. There are different strategies for angiogenesis intervention, based on the modulation of any of the different steps of the angiogenic process. In this chapter, we will provide an overview of the angiogenesis inhibitors isolated from marine sponges based on the available information regarding their primary targets or mechanism of action.

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IB05204, a dichloropyridodithienotriazine, inhibits angiogenesis in vitro and in vivo

Abstract: In the course of a blind screening program for inhibitors of angiogenesis, IB05204 (4,6 ¶:4 00 ,5 00

Cited by 19 publications

References 45 publications

Anti-Angiogenic and Anti-Inflammatory Properties of Kahweol, a Coffee Diterpene

Anti-Angiogenic and Anti-Inflammatory Properties of Kahweol, a Coffee Diterpene

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

Marine Sponge Derived Antiangiogenic Compounds

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