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Xanthohumol from hops prevents hormone-dependent tumourigenesis in vitro and in vivo.

Since the 1990s, interest in health-promoting effects of xanthohumol (XN) has increased constantly. This manuscript will review some of the published literature as well as novel findings on XN. In 2002, we identified XN as a potent cancer chemopreventive agent acting by multiple mechanisms relevant for the prevention of carcinogenesis. Although hops is commonly linked with phytoestrogenic effects, we identified XN as a pure estrogen antagonist. Interestingly, XN may also reduce the generation of estrogens by inhibition of the enzymatic activity of aromatase, which converts testosterone to estrogen. Anti-estrogenic effects of XN (100 mg/kg body weight/day) were confirmed in vivo in an uterotrophy assay with prepubertal rats. In two fertility studies, long-term treatment with XN did not cause any adverse effect on female reproduction and on the development of offspring when given either for four weeks prior to or during mating, gestation and nursing. Novel data indicate that XN (100 mg/kg body weight/day in drinking water) prevents dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats when given nine days prior to and for 16 weeks after the carcinogen. Tumour incidence was not influenced by XN treatment, but XN significantly reduced tumour multiplicity and tumour burden. XN (1000 mg/kg body weight/day injected subcutaneously for 14 days) also significantly reduced the growth of human breast cancer xenotransplants in immune-compromised mice and reduced tumour-induced neovascularization. Overall, these data demonstrate breast cancer preventive efficacy of XN. Multiple mechanisms, including modulation of DMBA metabolism, anti-estrogenic, anti-proliferative and anti-angiogenic activities may account for these effects and are under further investigation.