The characterization of bioactive resveratrol oligomers extracted from Vitis vinifera canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, trans-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 (IC₅₀) of 9.7 ± 0.4 µM at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC₅₀ of 47.8 ± 2.8 µM). By contrast, hopeaphenol (IC₅₀ of 13.1 ± 4.1 µM) and isohopeaphenol (IC₅₀ 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.

中文翻译：

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从葡萄中提纯天然二苯乙烯低聚物对人肝癌细胞的抗癌活性。

最近报道了从葡萄藤上提取的生物活性白藜芦醇低聚物的表征。在这里，我们筛选了其中的六种化合物（ampelopsin A，反式ε-viniferin，hopeaphenol，isohopeaphenol，R2-viniferin和R-viniferin）对人肝细胞癌（HCC）细胞株p53野生型HepG2和p53-null Hep3B。细胞毒性功效取决于细胞系。R2-viniferin是HepG2中毒性最高的二苯乙烯，在72 h时抑制浓度50（IC ₅₀）为9.7±0.4 µM，比白藜芦醇低3倍，而Hep3B的敏感性较低（IC ₅₀为47.8±2.8 µM）。 。相比之下，希望酚（IC ₅₀为13.1±4.1 µM）和异胡酚（IC26.0±3.0 µM中的_50个）对Hep3B的毒性更大。由于这些结果，并且由于它在未转化的HH4肝细胞中没有发挥大的细胞毒性，因此选择了R2-viniferin来研究其在HepG2中的作用机理。1,2-二苯乙烯趋向于在G2 / M处停止细胞周期，并且还增加了细胞内活性氧（ROS），半胱天冬酶3活性和Bax / Bcl-2蛋白的比率，表明细胞凋亡。R2-viniferin对HepG2的独特毒性鼓励对潜在机制的研究，以开发寡聚二苯乙烯作为具有特定遗传背景的抗HCC的治疗剂。