Resveratrol sensitizes HepG2 cells to TRAIL-induced apoptosis
Resveratrol sensitizes HepG2 cells to TRAIL-induced apoptosis
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DOI：
10.1097/cad.0000000000000128
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发表时间：
2014-10
影响因子：
2.3
通讯作者：
Masahiko Tameda;K. Sugimoto;K. Shiraki;Y. Inagaki;S. Ogura;Chika Kasai;Misao Yoneda;R. Okamoto;N. Yamamoto;Y. Takei;Masaaki Ito;T. Nobori
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文献类型：
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作者：
Masahiko Tameda;K. Sugimoto;K. Shiraki;Y. Inagaki;S. Ogura;Chika Kasai;Misao Yoneda;R. Okamoto;N. Yamamoto;Y. Takei;Masaaki Ito;T. Nobori
白藜芦醇是一种天然多酚，存在于多种植物中，包括葡萄、浆果和花生。白藜芦醇可以调节广泛的分子靶点，包括参与癌症信号通路的分子靶点。在这里，我们评估了白藜芦醇在肿瘤坏死因子相关凋亡诱导配体（TRAIL）中的作用，并在人肝癌细胞系HepG 2中研究了其分子机制。我们使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑测定来评估细胞活力，流式细胞术来分析细胞周期和凋亡，以及免疫印迹来检测蛋白质表达。白藜芦醇在100 mol/l或更高的浓度下降低细胞活力。在50 mol/L的浓度下，白藜芦醇诱导细胞周期的S期阻滞而无凋亡。此外，磷酸化AMPK以剂量依赖性方式显著增加。发现白藜芦醇协同增强TRAIL诱导的细胞凋亡。用50 mol/L白藜芦醇、10 ng/ml TRAIL和两种试剂处理的早期凋亡率分别为3.4、9.6和49.6%。白藜芦醇以剂量依赖性方式显著下调survivin的表达。总之，我们发现白藜芦醇可以通过下调生存素来增加TRAIL的敏感性。提示白藜芦醇联合TRAIL治疗肝癌可能是一种有效的新策略。
Resveratrol is a natural polyphenol found in a wide variety of plants, including grapes, berries, and peanuts. Resveratrol can modulate a wide spectrum of molecular targets, including those involved in cancer signaling pathways. Here, we evaluated the role of resveratrol in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and examined the molecular mechanisms in the human hepatocellular carcinoma cell line HepG2. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to assess cell viability, flow cytometry to analyze cell cycle and apoptosis, and immunoblotting to detect protein expression. Resveratrol decreased cell viability at a concentration of 100 mol/l or higher. At a concentration of 50 mol/l, resveratrol induced S phase arrest of the cell cycle without apoptosis. In addition, phospho-AMPK increased significantly in a dose-dependent manner. Resveratrol was found to synergistically augment TRAIL-induced apoptosis. The rates of early apoptosis were 3.4, 9.6, and 49.6% on treatment with 50 mol/l resveratrol, 10 ng/ml TRAIL, and both reagents, respectively. Resveratrol significantly downregulated the expression of survivin in a dose-dependent manner. In conclusion, we found that that resveratrol could augment TRAIL sensitivity by downregulating survivin. These results suggest that combination resveratrol with TRAIL may be an effective new strategy for the treatment of hepatocellular carcinoma.