Z Gastroenterol 2015; 53 - A4_24
DOI: 10.1055/s-0035-1568083

Ginkgo biloba differentially affects untransformed and malignant cells in the liver

C Czauderna 1, MP Dominguez 2, D Castven 1, LZ Rodriguez 1, M Herr 1, M Wörns 1, S Strand 1, LE Gomez-Quiroz 2, PR Galle 1, JU Marquardt 1
  • 1Universitätsmedizin Mainz, 1. Medizinische Klinik und Poliklinik, Mainz, Deutschland
  • 2Universidad Autónoma Metropolitana-Iztapalapa, Departamento de Ciencias de la Salud, Mexico City, Mexico

Ginkgo biloba (EGb) is a widely used botanical drug with diverse biological properties. Several reports indicate that EGb 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 EGb on human hepatocellular carcinoma cells as well as untransformed hepatocytes.

Human hepatoma cell lines, primary human HCC cells and immortalized human hepatocytes were exposed to various concentrations (0 – 1000 ug/ml) of EGb 761, a well-defined and quantified EGb leaf extract. Effects on proliferation, apoptosis and oxidative stress were evaluated after 72h of EGb exposure. Molecular changes were assessed by gene expression microrarrys, qRT-PCR, Western Blotting and confocal microscopy.

EGb 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 differential response of EGb on normal and malignant cells. Consistently, while EGb induced a significant reduction in both colony and sphere forming ability as well as reactive oxygen species (ROS) generation in hepatoma cells, the treatment caused no mentionable changes in untransformed cells. Mechanistically, anti-tumorigenic properties of EGb were exerted via inhibition of genes associated with cell cycle (e.g. CCND1, MAPK8), survival (e.g. AKT, MEK) and impaired redox potential (e.g. KEAP1).

EGb differentially affects hepatocytes and human hepatoma cells. While anti-tumorigenic and pro-apoptotic changes were induced in hepatoma cells, untransformed cells remained unaffected suggesting that EGb could be safely used for both preventive as well as therapeutic strategies. Future work will explore the molecular mechanism responsible for the observed differential response in normal and cancer cells.

Corresponding author: Marquardt, Jens U.

E-Mail: marquarj@uni-mainz.de