Abstract
Cytochalasans are a group of structurally diverse fungal polyketide-amino acid hybrid metabolites that exhibit diverse biological functions. Asperchalasine A was identified and isolated from an extract of the marine-derived fungus, Aspergillus. Asperchalasine A is a cytochalasan dimer which consists of two cytochalasan molecules connected by an epicoccine. This study investigated the potential antiangiogenic effects of Aspergillus extract and asperchalasine A, which significantly inhibited cell adhesion and tube formation in human umbilical vein endothelial cells (HUVECs). Aspergillus extract and asperchalasine A decreased the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 mRNA expression in a concentration-dependent manner. In addition, Aspergillus extract and asperchalasine A inhibited angiogenesis via downregulation of VEGF, p-p38, p-extracellular signal-regulated protein kinase (ERK), p-VEGFR-2, and p-Akt signaling pathways. Moreover, Aspergillus extract and asperchalasine A significantly inhibited the amount of blood vessel formation in fertilized chicken eggs using a chorioallantoic membrane assay. Our results provide experimental evidence of this novel biological activity of the potential antiangiogenic substances, Aspergillus extract, and asperchalasine A. This study also suggests that Aspergillus extract and its active component asperchalasine A are excellent candidates as adjuvant therapeutic substances for cancer prevention and treatment.
Highlights
All the cells of the human body need blood to supply oxygen and nutrients and to remove metabolic waste
We investigated the proliferation of human umbilical vein endothelial cells (HUVECs), which are commonly used as in vitro angiogenesis models, to determine the effects of the Aspergillus extract and asperchalasine A (Figure 1) on endothelial cell growth
Directional migration of endothelial cells is an essential element of angiogenesis [25], so we investigated the effect of treatment with Aspergillus extract and aspochalasine A on HUVEC migration
Summary
All the cells of the human body need blood to supply oxygen and nutrients and to remove metabolic waste. The microvascular network extends throughout the human body to maintain the homeostatic functions and metabolic activities of the cells [1]. Angiogenesis refers to a series of processes wherein new blood vessels are created from the existing blood vessels. It is required for fetal development, menstruation, and wound healing processes under normal conditions. Angiogenesis is known to be necessary in various diseases, such as cancer growth and metastasis, rheumatoid arthritis, and diabetic blindness [2,3]. Angiogenesis is a very tightly regulated phenomenon that is rarely observed under normal conditions.
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