The use of stilbenes has been proposed as an alternative to sulfur dioxide in wine. Provided the feasibility from a technological approach, the cytotoxicity of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99 extract) was assessed in the human cell lines HepG2 and Caco-2. In addition, the effects of the main stilbenes found in ST-99, trans-resveratrol and trans-epsilon-viniferin were studied, as well as its mixture. Similar cytotoxic effects were obtained in the exposures to trans-epsilon-viniferin, ST-99 and the mixture; however, transresveratrol alone exerted less toxicity. When HepG2 cells were exposed to trans-epsilon-viniferin, ST-99 and the mixture, the mean effective concentration (EC50) were 28.28 +/- 2.15, 31.91 +/- 1.55 and 29.47 +/- 3.54 mu g/mL, respectively. However, in the exposure to trans-resveratrol, the EC50 was higher 50 mu g/mL. The morphological study evidenced damage at ultrastructural level in HepG2 cells, highlighting the inhibition of cell proliferation and the induction of apoptosis. The type of interaction produced by trans-epsilon-viniferin and trans-resveratrol mixtures was assessed by an isobologram analysis using the CalcuSyn software, evidencing an antagonist effect. These data comprise a starting point in the toxicological assessment; further studies are needed in this field to assure the safety of the extract ST-99.