Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells
The characterization of bioactive resveratrol oligomers extracted from <i>Vitis vinifera</i> canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, <i>trans-</i>ε-viniferin, hopeaphenol, isohopeaphenol, R2-viniferin, and R-viniferin) for the...
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MDPI AG
2020-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/6/469 |
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| author | Iris Aja M. Begoña Ruiz-Larrea Arnaud Courtois Stéphanie Krisa Tristan Richard José-Ignacio Ruiz-Sanz |
| author_facet | Iris Aja M. Begoña Ruiz-Larrea Arnaud Courtois Stéphanie Krisa Tristan Richard José-Ignacio Ruiz-Sanz |
| author_sort | Iris Aja |
| collection | DOAJ |
| description | The characterization of bioactive resveratrol oligomers extracted from <i>Vitis vinifera</i> canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, <i>trans-</i>ε-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 (IC<sub>50</sub>) of 9.7 ± 0.4 µM at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC<sub>50</sub> of 47.8 ± 2.8 µM). By contrast, hopeaphenol (IC<sub>50</sub> of 13.1 ± 4.1 µM) and isohopeaphenol (IC<sub>50</sub> of 26.0 ± 3.0 µM) 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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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T19:26:45Z |
| publishDate | 2020-06-01 |
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| series | Antioxidants |
| spelling | doaj.art-7051a5656b6547eabfbeca41f9a0e8232023-11-20T02:29:07ZengMDPI AGAntioxidants2076-39212020-06-019646910.3390/antiox9060469Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma CellsIris Aja0M. Begoña Ruiz-Larrea1Arnaud Courtois2Stéphanie Krisa3Tristan Richard4José-Ignacio Ruiz-Sanz5Free Radicals and Oxidative Stress (FROS) research group of the Department of Physiology, Medicine and Nursing School, University of the Basque Country UPV/EHU, 48940 Leioa, SpainFree Radicals and Oxidative Stress (FROS) research group of the Department of Physiology, Medicine and Nursing School, University of the Basque Country UPV/EHU, 48940 Leioa, SpainUniv. Bordeaux, INRAE, UR Œnologie, EA 4577, USC 1366, ISVV, 210 Chemin de Leysotte, F 33882 Villenave d’Ornon, FranceUniv. Bordeaux, INRAE, UR Œnologie, EA 4577, USC 1366, ISVV, 210 Chemin de Leysotte, F 33882 Villenave d’Ornon, FranceUniv. Bordeaux, INRAE, UR Œnologie, EA 4577, USC 1366, ISVV, 210 Chemin de Leysotte, F 33882 Villenave d’Ornon, FranceFree Radicals and Oxidative Stress (FROS) research group of the Department of Physiology, Medicine and Nursing School, University of the Basque Country UPV/EHU, 48940 Leioa, SpainThe characterization of bioactive resveratrol oligomers extracted from <i>Vitis vinifera</i> canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, <i>trans-</i>ε-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 (IC<sub>50</sub>) of 9.7 ± 0.4 µM at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC<sub>50</sub> of 47.8 ± 2.8 µM). By contrast, hopeaphenol (IC<sub>50</sub> of 13.1 ± 4.1 µM) and isohopeaphenol (IC<sub>50</sub> of 26.0 ± 3.0 µM) 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.https://www.mdpi.com/2076-3921/9/6/469stilbeneresveratrol oligomersnatural productpolyphenolanticancer activityHepG2 cells |
| spellingShingle | Iris Aja M. Begoña Ruiz-Larrea Arnaud Courtois Stéphanie Krisa Tristan Richard José-Ignacio Ruiz-Sanz Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells Antioxidants stilbene resveratrol oligomers natural product polyphenol anticancer activity HepG2 cells |
| title | Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells |
| title_full | Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells |
| title_fullStr | Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells |
| title_short | Screening of Natural Stilbene Oligomers from <i>Vitis vinifera</i> for Anticancer Activity on Human Hepatocellular Carcinoma Cells |
| title_sort | screening of natural stilbene oligomers from i vitis vinifera i for anticancer activity on human hepatocellular carcinoma cells |
| topic | stilbene resveratrol oligomers natural product polyphenol anticancer activity HepG2 cells |
| url | https://www.mdpi.com/2076-3921/9/6/469 |
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