Antiangiogenic Properties of Lupulone, a Bitter Acid of Hop Cones

Abstract

Background: Angiogenesis is the result of intricate steps regulated by the balance between agonistic and antagonistic effectors. Disturbance of this balance leads to an ‘angiogenic’ switch critical for tumor development. Materials and Methods: Using human umbilical vein endothelial cells (HUVEC) the effects of lupulone were analyzed on proliferation induced by angiogenic growth factors, transmembrane cell migration toward fibronectin and formation of a network of tubular-like structures on Matrigel. Results: Lupulone (2.5-50 μg/ml) induced a concentration-dependent inhibition of HUVEC proliferation and chemotaxis. Lupulone caused a significant reduction of closed capillary-like structures in Matrigel indicating a strong inhibitory effect on neovascularisation. In mice receiving lupulone (20 mg/kg/day) in drinking water for 21 days, new vessel formation was reduced by 50% in matrigel plugs implanted under the skin when compared with controls. Conclusion: The present data demonstrate that lupulone is able to inhibit angiogenesis in vitro and in vivo. Lupulone emerges as a potential chemopreventive agent when considering its strong antiangiogenic properties.