Antiangiogenic properties of lupulone, a bitter acid of hop cones.
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.


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 microg/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.


CONCLUSIONS
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.
Siegel
Luz
L
Université Louis Pasteur EA 3430, Faculté de Médecine, Laboratoire de Recherche sur l'Angiogenèse, Strasbourg, France.
Miternique-Grosse
Anne
A
Griffon
Christian
C
Klein-Soyer
Claudine
C
Lobstein
Annelise
A
Raul
Francis
F
Stephan
Dominique
D
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007797:Laminin; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans; D013729:Terpenes / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology
D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D013729:Terpenes; C059485:matrigel; D003094:Collagen; C008299:lupulon