Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597474
4. Tumors/Liver Surgery
Georg Thieme Verlag KG Stuttgart · New York

Ginkgo biloba induces different gene expression signatures of oncogenic pathways in malignant and non-malignant cells in the liver

Authors

  • C Czauderna

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • M Palestino Dominguez

    2   Universidad Autónoma Metropolitana-Iztapalapa, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Mexico city, Mexico

  • D Castven

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • M Herr

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • D Strand

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • D Wilhelm

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • S Strand

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • S Heilmann

    3   University of Bonn, Institute of Human Genetics, Department of Genomics, Life & Brain Center, Bonn, Germany

  • L Gomez-Quiroz

    2   Universidad Autónoma Metropolitana-Iztapalapa, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Mexico city, Mexico

  • PR Galle

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany

  • JU Marquardt

    1   Johannes Gutenberg University, Department of Medicine I, Mainz, Germany
Further Information
Czauderna, Carolin

Publication History

Publication Date:
19 December 2016 (online)

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Background: The Ginkgo biloba extract, EGb761, is a herbal supplement obtained from the leaves of the ginkgo tree with diverse biological properties. Recent studies indicate that EGb761 confers both preventive effects as well as anti-tumor effects 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. 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. 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 different gene expression signatures by EGb761 treatment in each cell line. Transcriptomic changes predominantly affected key oncogenic properties resembling in cell growth and proliferation as well as NRF2-mediated 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 by modulating oncogenic pathways. 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.


No conflict of interest has been declared by the author(s).

Czauderna, Carolin