Hop bitter acids inhibit tumorigenicity of hepatocellular carcinoma cells in vitro

Oncol Rep. 2012 Oct;28(4):1423-8. doi: 10.3892/or.2012.1925. Epub 2012 Jul 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / chemistry
  • Acids / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Aspartate Aminotransferases / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cyclohexanones / pharmacology
  • Cyclohexenes / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Humulus / chemistry*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Terpenes / pharmacology
  • Transcription Factor AP-1 / metabolism
  • Tumor Cells, Cultured


  • Acids
  • Antineoplastic Agents, Phytogenic
  • Cyclohexanones
  • Cyclohexenes
  • NF-kappa B
  • Plant Extracts
  • Terpenes
  • Transcription Factor AP-1
  • cohumulone
  • adhumulone
  • colupulone
  • lupulon
  • Aspartate Aminotransferases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • humulon