title: Hop bitter acids inhibit tumorigenicity of hepatocellular carcinoma             cells in vitro.
abstract: Bitter acids (BAs) from the hop plant Humulus lupulus L. exhibit multiple             beneficial biological properties with promising effects in cancer therapy and             prevention, but information regarding the effects on hepatocellular carcinoma             (HCC) is missing. Here, we used two different hop bitter acid extracts enriched             for either α-acids or β-acids to obtain insight into whether biological activity             varies between these two groups of BAs. At a concentration of 25 µg/ml, only the             β-acid rich started to induce aspartate transaminase (AST) release, and a significant             increase was detected with 50 µg/ml of both extracts. Already at lower concentrations             both extracts led to a dose-dependent inhibition of proliferation, and migration             was suppressed at a concentration as low as 5 µg/ml in HCC cells. The focus on             different 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-acid             rich 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 functional             nutrients for both prevention and treatment of HCC.
authors: Department of Internal Medicine I, University Hospital Regensburg, and Department of Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors: Michael
authors: M
authors: Saugspier
authors: Christoph
authors: C
authors: Dorn
authors: Barbara
authors: B
authors: Czech
authors: Manfred
authors: M
authors: Gehrig
authors: Jörg
authors: J
authors: Heilmann
authors: Claus
authors: C
authors: Hellerbrand
mesh_terms: D000143:Acids / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003512:Cyclohexanones / Q000494:pharmacology; D053138:Cyclohexenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000143:Acids; D000972:Antineoplastic Agents, Phytogenic; D003512:Cyclohexanones; D053138:Cyclohexenes; D016328:NF-kappa B; D010936:Plant Extracts; D013729:Terpenes; D018808:Transcription Factor AP-1; C442487:cohumulone; C442488:adhumulone; C075356:colupulone; C008299:lupulon; D001219:Aspartate Aminotransferases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C007966:humulon