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Bitter acids (BAs) from the hop plant Humulus lupulus L. exhibit multiplebeneficial biological properties with promising effects in cancer therapy andprevention, but information regarding the effects on hepatocellular carcinoma(HCC) is missing. Here, we used two different hop bitter acid extracts enrichedfor either α-acids or β-acids to obtain insight into whether biological activityvaries between these two groups of BAs. At a concentration of 25 µg/ml, only theβ-acid rich started to induce aspartate transaminase (AST) release, and a significantincrease was detected with 50 µg/ml of both extracts. Already at lower concentrationsboth extracts led to a dose-dependent inhibition of proliferation, and migrationwas suppressed at a concentration as low as 5 µg/ml in HCC cells. The focus ondifferent signaling pathways revealed an inhibition of ERK1/2 phosphorylation,downregulation of AP-1 activity and an alleviation of nuclear factor κB (NFκB)activity in HepG2 cells incubated with 5 µg/ml of both extracts, whereby the β-acidrich extract showed more pronounced effects. In conclusion, we identified ERK1/2,AP-1 and NFκB, which are important factors in tumor development and progression,as targets of hop BAs. Thus, these data suggest the potential use of BAs as functionalnutrients for both prevention and treatment of HCC.

Hop bitter acids inhibit tumorigenicity of hepatocellular carcinoma cells in vitro