Xanthohumol, a prenylated chalcone derived from hops, inhibits proliferation, migration and interleukin-8 expression of hepatocellular carcinoma cells

Xanthohumol (XN) is the major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. It has been discussed as a scavenger of reactive oxygen species and exerts anti-inflammatory and anti-cancer effects. However, the impact on hepatocellular carcinoma (HCC) cells and potential adverse effects on non-tumorous hepatocytes have not been examined so far.

Methods and Results: XN at a concentration of 25µM induced apoptosis in two HCC cell lines (HepG2 and Huh7). Furthermore, XN repressed proliferation and migration, as well as TNF induced NFkappaB activity and interleukin-8 expression in both cell lines at even lower concentrations. In contrast, XN concentrations up to 100µM did not affect viability of primary human hepatocytes in vitro. Safety of XN application at a concentration of up to 1,000mg XN /kg body weight was confirmed in an in vivo feeding model, where histopathological analysis and biochemical serum analysis confirmed normal organ function. Furthermore, serum glucose levels and hepatic glycogen content as well as hepatic CYP2E1 mRNA expression levels were unaffected by xanthohumol treatment.

Conclusion: Xanthohumol has the potential to ameliorate different pro-tumorigenic mechanisms known to promote HCC progression, suggesting its potential use as functional nutrient to prevent development of HCC or as promising therapeutic agent, that selectively affects cancer cells. Particularly, hepatotoxic effects of XN could be ruled out confirming a good safety profile of XN as prerequisite for further studies in humans.