Cancer Chemopreventive Potential of Humulones and Isohumulones (Hops α- and Iso-α-acids): Induction of NAD(P)H:Quinone Reductase as a Novel Mechanism

Phytochemical analysis and chemopreventive testing of a special “α-/β-acid free” hops extract led to the identification of isohumulones (hops iso-α-acids) as potent inducers of NAD(P)H:quinone reductase (QR) activity. CD values (concentrations required to double the specific activity of QR in Hepa1c1c7 cell culture) were in the range of 1.3 to 10.2 μg/mL, with CD value of trans-isohumulone < cis-isoadhumulone < cis-isocohumulone < cis-isohumulone (+ trans-isoadhumulone). Humulones (hops α-acids) were equally active with CD values of 3.4 to 7.6 μg/mL. However, these activities were accompanied by cytotoxicity. Cohumulinone and humulinone, oxidation products of coand n-humulone, were inactive. We further identified isohumulones as potent inhibitors of lipopolysaccharide-induced inducible nitric oxide synthase (iNOS) activity in Raw264.7 cell culture, with IC50 values of 5.9 – 18.4 μg/mL. Humulones and humulinones were inactive at concentrations < 20 μg/mL. These results indicate that isohumulones, which are considered as the most abundant class of polyphenols in beer, should by further investigated for chemopreventive efficacy in animal models.