Z Gastroenterol 2016; 54 - KV322
DOI: 10.1055/s-0036-1587098

Ginkgo biloba impairs tumorigenic potential of malignant cells in the liver through deregulation of multiple molecular pathways

C Czauderna 1, MP Dominguez 2, D Castven 1, LZ Rodriguez 1, D Strand 3, D Wilhelm 1, S Strand 3, S Heilmann 4, L Gomez-Quiroz 2, PR Galle 3, JU Marquardt 1
  • 1Johannes Gutenberg University, Department of Medicine I; Lichtenberg Research Group “Molecular Hepatocarcinogenesis”, Mainz, Deutschland
  • 2Universidad Autónoma Metropolitana-Iztapalapa, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Mexico-Stadt, Mexico
  • 3Johannes Gutenberg University, Department of Medicine I, Mainz, Deutschland
  • 4University of Bonn, Institute of Human Genetics, Department of Genomics, Life & Brain Center, Bonn, Deutschland

Background and aims: Ginkgo biloba (EGb761) is a widely used botanical drug with diverse biological properties. Several reports indicate that EGb761 confers both preventive effects as well as anti-tumorigenic properties in a variety of tumors, including hepatocellular carcinoma (HCC). We here evaluate the functional and mechanistic effects of EGb761 on human hepatocellular carcinoma cells as well as untransformed hepatocytes.

Methods: Human hepatoma cell lines, primary human HCC cells and immortalized human hepatocytes were exposed to various concentrations (0 – 1000 ug/ml) of EGb761, a well-defined and quantified EGb leaf extract. Effects on proliferation and apoptosis were evaluated after 72h of EGb761 exposure. Molecular changes were assessed by gene expression microrarrays and Western Blotting.

Results: EGb761 administration significantly impaired proliferation and induced apoptosis in hepatoma cells as well as hepatocytes. However, median IC50 for the hepatoma cells was dramatically lower than in hepatocytes suggesting a different response of EGb761 on normal and malignant cells. Consistently, while EGb761 induced a significant reduction in both colony and sphere forming ability in hepatoma cells, the treatment caused no mentionable changes in untransformed cells. Global gene expression analyses identified genes differentially regulated by EGb761 treatment in each cell line. Transcriptomic changes predominantly affected key oncogenic properties resembling in cell growth and proliferation as well as oxidative stress response in hepatoma cells. Furthermore, comparative analyses of the affected molecular pathways in hepatoma cells and hepatocytes identified a differential regulation of MAPK/ERK and PI3K/AKT/mTOR signaling. In consequence, regulation of eIF4 and p70SK6 was affected in hepatoma cells possibly leading to a disruption of cell growth by impaired protein biosynthesis.

Conclusion: EGb761 differently affects hepatocytes and human hepatoma cells. While anti-tumorigenic and pro-apoptotic changes were induced in hepatoma cells, untransformed cells remained unaffected suggesting that EGb761 could be safely used for both preventive as well as therapeutic strategies.