Z Gastroenterol 2012; 50 - P5_11
DOI: 10.1055/s-0031-1295967

Chemotherapeutic use of Resveratrol on liver cancer cell lines cause damage on primary human hepatocytes

G Damm 1, L Hao 2, S Ehnert 3, A Blankenstein 1, AK Nüssler 3, D Knobeloch 1, M Glanemann 1
  • 1Charite, Department of General, Visceral and Transplantation Surgery, Berlin
  • 2Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 3Department of Traumatology and Reconstructive Surgery, BG-Trauma and Medical Centre Tübingen, Eberhard Karls University Tübingen, Tübingen

Apart from cardiac diseases, cancer is a major cause of morbidity and mortality worldwide. The resection of the tumor is a common therapeutic treatment. Alternative therapy with chemotherapeutics has often not had a selective effect on the tumor tissue and patients suffer from various side effects. Due to the limited efficiency of chemotherapy, there is growing interest in improving anticancer drugs. Resveratrol (RES), a naturally occurring polyphenol is of increasing relevance since anti-inflammatory and anti-carcinogenic properties were proven in various in vitro and in vivo studies. The anti carcinogenetic action of RES was shown in colon, breast, prostate, ovarian and liver cancer cell lines. In the literature, RES concentrations of between 50 and 300µM are described as having a cytotoxic effect on cancer cells. RES effects on normal human liver cells have not been documented yet. In the present work we will show that the effective concentration range of RES showing an apoptotic effect on liver cell lines is causing toxic effects on primary human hepatocytes (pHH) as well. Between 50–300µM RES caused a strong LDH release from SkHep1 cells, while pHH showed an increasing loss in membrane integrity starting at 100µM. Thus, the distinct effect on tumor cell lines of RES is not selective. This complicates the use as a liver tumor therapeutic drug due to a small therapeutic non-toxic window. Therefore, we tested its practicability as a sensitizer for tumor cells using non-toxic concentrations in combination with the widely used chemotherapeutic agent 5-fluorouracil (5-FU). However, the pretreatment with RES could not lower the IC50 value of 5-FU significantly. Furthermore, RES only induced the known cell cycle arrest in the S-phase of SkHep1 cells in low concentrations and up to 48h of treatment. In both SkHep1 cells and pHH no cell death was detected, regardless of p53 activation. Thus, it is unlikely that RES can be used as a possible anti-liver cancer drug.