Cheiradone: a vascular endothelial cell growth factor receptor antagonist

Abstract

Background: Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing) and pathological conditions (tumour development). Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are the major angiogenic regulators. We have identified a natural product (cheiradone) isolated from a Euphorbia species which inhibited in vivo and in vitro VEGFstimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation) and in vivo (the chick chorioallantoic membrane) models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC 50 ) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.

Thermostable small-molecule inhibitor of angiogenesis and vascular permeability that suppresses a pERK-FosB/ΔFosB–VCAM-1 axis

“…BAECs were used for this purpose since HMEC-1 cells lack VEGFR-2 (Flk/KDR) and only weakly migrate toward VEGF ( 25 ). BAECs, on the other hand, express VEGFR-2 ( 26 ) and migrate to VEGF-A ( 27 ). In contrast, neither BT3 nor PD98059 [allosteric mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor], imatinib (tyrosine kinase inhibitor), or tofacitinib (Janus kinase inhibitor) had an inhibitory effect at the same concentration ( Fig.…”

Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis

“…We have shown using other plant-derived natural products that increased polarity correlates with effectiveness of growth factor inhibition. For example, the ability of sesterterpenes to inhibit FGF-2-induced angiogenesis [ 18 ] and cheiradone to inhibit VEGF [ 19 ] increased with polarity.…”

The Evolving Role of Natural Products from the Tropical Rainforests as a Replenishable Source of New Drug Leads

“…However, cheiradone had no effect on fibroblast growth factor (FGF)-2 or epidermal growth factor (EGF) activity. [160]. Recently, a study using a transgenic mouse model of melanoma exhibited that the anticancer effects of popular kampo medicine were mediated by an improved antigenspecific antitumor cytotoxic T-lymphocyte response [151,161].…”