Aja Iris, Ruiz-Larrea M Begoña, Courtois Arnaud, Krisa Stéphanie, Richard Tristan, Ruiz-Sanz José-Ignacio
Free 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, Spain.
Univ. Bordeaux, INRAE, UR Œnologie, EA 4577, USC 1366, ISVV, 210 Chemin de Leysotte, F 33882 Villenave d'Ornon, France.
Antioxidants (Basel). 2020 Jun 1;9(6):469. doi: 10.3390/antiox9060469.
The characterization of bioactive resveratrol oligomers extracted from canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, 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) of 9.7 ± 0.4 µM at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC of 47.8 ± 2.8 µM). By contrast, hopeaphenol (IC of 13.1 ± 4.1 µM) and isohopeaphenol (IC 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.
最近有报道对从葡萄茎中提取的生物活性白藜芦醇低聚物进行了表征。在此，我们筛选了其中六种化合物（蛇葡萄素A、ε-葡萄素、去氢双儿茶素、异去氢双儿茶素、R2-葡萄素和R-葡萄素）对人肝细胞癌（HCC）细胞系p53野生型HepG2和p53缺失型Hep3B的细胞毒性活性。细胞毒性效力取决于细胞系。R2-葡萄素是对HepG2毒性最大的芪类化合物，在72小时时的半数抑制浓度（IC）为9.7±0.4μM，比白藜芦醇低3倍，而Hep3B对其敏感性较低（IC为47.8±2.8μM）。相比之下，去氢双儿茶素（IC为13.1±4.1μM）和异去氢双儿茶素（IC为26.0±3.0μM）对Hep3B的毒性更大。基于这些结果，并且由于它在HH4未转化肝细胞中未表现出很大的细胞毒性，因此选择R2-葡萄素研究其在HepG2中的作用机制。该芪类化合物倾向于使细胞周期停滞在G2/M期，还增加了细胞内活性氧（ROS）、半胱天冬酶3活性以及Bax/Bcl-2蛋白的比率，表明发生了细胞凋亡。R2-葡萄素对HepG2的独特毒性促使人们对其潜在机制进行研究，以便将该低聚芪开发成针对具有特定遗传背景的HCC的治疗药物。
