Xanthohumol: Investigations on breast cancer chemopreventive potential

We have identified Xanthohumol, a prenylated chalcone from hop, as a most promising cancer chemopreventive agent with protective mechanisms in all stages of carcinogenesis. As a first indication of chemopreventive potential, xanthohumol prevented chemically-induced preneoplastic lesions in an ex vivo mouse mammary organ culture model at about 200-fold lower concentrations than resveratrol found in red wine (Gerhauser et al., MCT 2002).

Based on these results, we are currently investigating the in vivo breast cancer chemopreventive efficacy of xanthohumol. Initially, the maximally tolerated dose, the best route of application, bioavailability, organ distribution, in vitro and in vivo metabolism and its influence on reproduction (risk assessment) have been determined (Nookandeh et al., 2004; Ruefer et al., 2005; Hussong et al., 2005). For these studies, 14C-labeled xanthohumol has be generated and provided by a cooperation partner (Berwanger et al., 2005).

We will further characterize in vivo mechanisms of action of xanthohumol at the biochemical and molecular level in comparison with its broad spectrum of in vitro activities, with special focus on modulation of carcinogen metabolism, anti-oxidant potential, anti-inflammatory mechanisms and anti-proliferative activity. Subsequently, we will measure the potential of xanthohumol to reduce the number and size of chemically-induced mammary tumors in rats.

funded by the DFG as a part of the DFG FlavoNet