Hop bitter acids inhibit tumorigenicity of hepatocellular carcinoma cells

Bitter acids (BA) are the major component of the female inflorescences of the hop plant humulus lupulus. BA are added to beer because of their antibacterial effect and their typical bitter taste, and recent studies revealed that BA are multipotent bioactive compounds that exhibit anti-carcinogenic effects.

The aim of the present study was assess the effect of BA on hepatocellular carcinoma (HCC).

Methods and Results: Different HCC cell lines (Hep3B, HepG2, PLC) were incubated with bitter acids purified from a CO2 hop extract at various concentrations. Beginning at a concentration of 25µg/ml BA induced cytotoxic effects in all 3 HCC cell lines as evidenced by morphological changes and LDH release. However, already at concentrations as low as 5µg/ml BA significantly impaired proliferation and migration of HCC cells in functional in vitro analysis. The transcription factors ERK- and NFkappaB are known to promote tumorigenicity of HCC cells in vitro and in vivo, and of note, both factors were dose-dependently inhibited by BA in HCC cells.

Conclusion: Bitter acids have the potential to ameliorate different pro-tumorigenic mechanisms known to promote HCC progression. Previous studies have shown the safety of even long term application of hop extracts in man, and thus, our data suggest the potential use of this natural hop compound as therapeutic agent in HCC.