Istituto Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche, 83100 Avellino, Italy.
Food Chem Toxicol. 2013 Oct;60:377-84. doi: 10.1016/j.fct.2013.07.078. Epub 2013 Aug 6.
Until recently, the supposed preventive effects of red wine against cardiovascular diseases, the so-called "French Paradox", has been associated to its antioxidant properties. The interest in the anticancer capacity of polyphenols present in red wine strongly increased consequently to the enormous number of studies on resveratrol. In this study, using lyophilized red wine, we present evidence that its anticancer effect in a cellular model is mediated by apoptotic and autophagic cell death. Using a human osteosarcoma cell line, U2Os, we found that the lyophilized red wine was cytotoxic in a dose-dependent manner with a maximum effect in the range of 100-200 μg/ml equivalents of gallic acid. A mixed phenotype of types I/II cell death was evidenced by means of specific assays following treatment of U2Os with lyophilized red wine, e.g., autophagy and apoptosis. We found that cell death induced by lyophilized red wine proceeded through a mechanism independent from its anti-oxidant activity and involving the inhibition of PI3K/Akt kinase signaling. Considering the relative low concentration of each single bioactive compound in lyophilized red wine, our study suggests the activation of synergistic mechanism able to inhibit growth in malignant cells.
直到最近,红葡萄酒预防心血管疾病的所谓“法国悖论”的假设预防作用,一直与其抗氧化特性有关。由于大量关于白藜芦醇的研究,人们对红葡萄酒中多酚类物质的抗癌能力产生了浓厚的兴趣。在这项研究中,我们使用冻干红葡萄酒,证明了其在细胞模型中的抗癌作用是通过细胞凋亡和自噬性细胞死亡介导的。使用人骨肉瘤细胞系 U2Os,我们发现冻干红葡萄酒具有剂量依赖性的细胞毒性,最大效应在 100-200μg/ml 没食子酸当量范围内。通过对 U2Os 用冻干红葡萄酒处理后进行特定的检测,证实了 I/II 型细胞死亡的混合表型,例如自噬和凋亡。我们发现,冻干红葡萄酒诱导的细胞死亡是通过一种独立于其抗氧化活性的机制进行的,该机制涉及到对 PI3K/Akt 激酶信号的抑制。考虑到冻干红葡萄酒中每种单一生物活性化合物的相对低浓度,我们的研究表明激活协同机制能够抑制恶性细胞的生长。