Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF-κB and Akt as targets

SPECIFIC AIMSXanthohumol (XN) is a flavonoid of the chalcone chemical class isolated from hop ‘cones’, the female inflorescences of the hop plant (Humulus lupulus L.). It is largely used in the brewing industry as a preservative and flavoring agent. Several natural compounds of plant origin and dietary components, have been shown to have cancer chemoprevention and/or therapeutic activities. We have shown that inhibition of angiogenesis is a mechanism by which dietary components prevent cancer, a concept we termed “angioprevention.” XN has several properties that suggest it may be an angiopreventive agent. Here we show for the first time that XN can inhibit growth of a vascular tumor in vivo; histopathology indicated that much of this effect was by blocking angiogenesis which was confirmed by in vitro and in vivo analyses. XN represses both the NF-κB and Akt pathways in endothelial cells, indicating that they are major targets in the molecular mechanism of XN. Our data provide the basis for clinical tumor ...