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Screening of natural stilbene oligomers from Vitis vinifera for anticancer activity on human hepatocellular carcinoma cells

Abstract : The characterization of bioactive resveratrol oligomers extracted fromVitis viniferacanes has been recently reported. Here, we screened six of these compounds (ampelopsin A,trans-epsilon-viniferin, hopeaphenol, isohopeaphenol, R2-viniferin, and R-viniferin) for their cytotoxic activity to human hepatocellular carcinoma (HCC) cell lines p53 wild-type HepG2 and p53-null Hep3B. The cytotoxic efficacy depended on the cell line. R2-viniferin was the most toxic stilbene in HepG2, with inhibitory concentration 50 (IC50) of 9.7 +/- 0.4 mu M at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC(50)of 47.8 +/- 2.8 mu M). By contrast, hopeaphenol (IC(50)of 13.1 +/- 4.1 mu M) and isohopeaphenol (IC(50)of 26.0 +/- 3.0 mu M) were more toxic to Hep3B. Due to these results, and because it did not exert a large cytotoxicity in HH4 non-transformed hepatocytes, R2-viniferin was selected to investigate its mechanism of action in HepG2. The stilbene tended to arrest cell cycle at G2/M, and it also increased intracellular reactive oxygen species (ROS), caspase 3 activity, and the ratio of Bax/Bcl-2 proteins, indicative of apoptosis. The distinctive toxicity of R2-viniferin on HepG2 encourages research into the underlying mechanism to develop the oligostilbene as a therapeutic agent against HCC with a particular genetic background.
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Iris Aja, M. Begoña Ruiz-Larrea, Arnaud Courtois, Stéphanie Krisa, Tristan Richard, et al.. Screening of natural stilbene oligomers from Vitis vinifera for anticancer activity on human hepatocellular carcinoma cells. Antioxidants , MDPI, 2020, 9 (6), pp.1-14. ⟨10.3390/antiox9060469⟩. ⟨hal-02912069⟩

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