Abstract
BackgroundAngiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis. Therefore, many efforts have been made to develop effective anti-angiogenic agents as anticancer therapeutics. In the current study, we investigated the anti-angiogenic potential of an ethanol extract of Annona atemoya seeds (EEAA) in vitro and in vivo.MethodsThe anti-angiogenic potential of EEAA was evaluated using various in vitro/in vivo models, including cell proliferation, migration, and tube formation by human umbilical vascular endothelial cells (HUVECs); a Matrigel plug assay; and tumor-induced angiogenesis. The expression of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) was investigated using reverse transcription-polymerase chain reaction, immunoassays, and western blotting.ResultsEEAA was able to significantly inhibit the angiogenic properties of HUVECs in vitro as well as angiogenic factor-induced blood vessel formation in vivo. EEAA down-regulated the expression of VEGF and HIF-1alpha/2alpha at the mRNA and protein levels, respectively, in cancer cells under hypoxic conditions.ConclusionsEEAA shows a strong anti-angiogenic potential in both in vitro and in vivo systems, and we suggest that EEAA may be a valuable herbal source for anticancer drug development.
Highlights
Angiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis
ethanol extract of Annona atemoya seeds (EEAA) inhibits endothelial function-related angiogenesis in vitro and in vivo The effects of EEAA on the angiogenic properties mediated by Human umbilical vascular endothelial cells (HUVEC) were evaluated in vitro
In addition HUVECs failed to form three dimensional tube like structure on the matrix supports in the presence of EEAA (Figure 2D)
Summary
Angiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis. We investigated the anti-angiogenic potential of an ethanol extract of Annona atemoya seeds (EEAA) in vitro and in vivo. Crude extracts of A. atemoya seeds can potentially be used in botanical insecticides, and bullatacin, which is an annonaceous acetogenin isolated from Annona atemoya, has been reported to induce apoptotic cell death in the human 2.2.15 hepatocarcinoma cell line by reducing intracellular cAMP and cGMP levels [14,15]. The effect of the ethanol extract of Annona atemoya seeds (EEAA) on angiogenesis and its underlying mechanism remain unknown. We demonstrated that EEAA exhibits anti-angiogenic potential both in vitro and in vivo. This report is the first to demonstrate the anti-angiogenic effect of a crude extract of A. atemoya seeds
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