In accordance with the results of the LDH release assay, no significant increase was observed for any concentration tested. To allow a direct comparison between tumor and non-malignant cells, a SRB assay was performed after 96 h of resveratrol treatment. Consistent with the LDH and AST results, no signs of toxicity for resveratrol were observed. Taken together, resveratrol seemed to be well tolerated by PHH at concentrations that were found to induce a severe reduction of viability in different tumor cell lines. Epigenetic drugs, especially HDACi, can cause embryotoxic effects. Therefore, in addition to the evaluation of the cytotoxicity mediated by resveratrol in non-malignant hepatocytes, we performed an embryotoxicity assay. Cancer cells are characterized by various molecular changes. It is believed that especially epigenetic 1,9-Dideoxyforskolin modifications play a crucial role in tumor development and maintenance. In this context, the inhibition of HDAC enzymes has become an important therapeutic target and has shown promising results in cancer therapy. So far, only two HDACi are approved by the FDA for clinical use. Although some HDACi are currently tested in clinical trials, the identification of new inhibitors with low side effects has become of major interest. In recent years, a growing number of nutrients and dietary substances with chromatin effects. Resveratrol modulates multiple cellular signalling pathways and has demonstrated to be epigenetically active. Due to the pleiotropic biological activities of resveratrol, we were interested in a possible resveratrol-mediated modulation of the classical HDAC enzyme families I, II and IV, which play an eminent role in tumor formation and growth. By in silico docking 7-Chlorokynurenic acid analysis we detected a resveratrol-mediated inhibition of HDAC enzymes of classes I and II. Structure-activity studies showed that resveratrol fits into the binding pocket of HDACs and interacts with the zinc ion as well as other amino acid residues forming the active site. As demonstrated by established HDACi like SAHA and TSA, binding and interaction with the catalytic center are important features for HDACi activity. The predicted inhibition potential was approved in vitro by a standardized HDAC inhibitor screening assay as well as profiling studies for all known classical human HDAC enzymes. According to our in vitro and in silico results we postulate that resveratrol is a pan- HDACi. The observed weak HDACi potential of resveratrol however was not surprising and is in line with the hypothesis that nutritional HDACi are expected to exert moderate inhibitory activities. On the other hand, in mice resveratrol is described as an activator of SIRT1, a member of the mammalian sirtuins or HDAC class III, respectively.