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Apoptosis-inducing factor and caspase-dependent apoptotic pathways triggered by different grape seed extracts on human colon cancer cell line Caco-2

机译:不同葡萄籽提取物对人结肠癌细胞系Caco-2诱导的凋亡诱导因子和caspase依赖性凋亡途径

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摘要

Consumption of grape seed extract (GSE) is widely marketed as a dietary supplement and is considered safe for human health. Nevertheless, the analytical composition of GSE from different grape cultivars, growing in special agronomic constraints, differs greatly in flavan-3-ols content. The major concern with GSE studies is a lack of availability of uniformly standardised preparations, which raises an important question whether different GSE samples have comparable activity and trigger the same mechanisms of action on a given biological system. Therefore, it is tempting to speculate that GSE, obtained from different cultivars, could exert differentiated anticancer effects. The focus of the present study is to determine the selective biological efficacy of GSE obtained from three different sources on the human colon cancer cell line Caco-2. Irrespective of its source, high doses of GSE induced a significant inhibition on Caco-2 cell growth. Moreover, apoptosis was enhanced through both caspase-dependent and caspase-independent mechanisms, leading to an early apoptosis-inducing factor release and, further, to a dramatic increase in caspase 7 and 3 activity. However, a significant difference in apoptotic rates induced by the three grape sources clearly emerged when treating cancer cells with low and intermediate GSE concentrations (25 and 50 mu g/ml).
机译:食用葡萄籽提取物(GSE)作为膳食补充剂被广泛销售,被认为对人体健康安全。然而,来自不同葡萄品种的GSE的分析成分,在特殊的农艺学限制下生长,其flavan-3-ols含量差异很大。 GSE研究的主要问题是缺乏统一标准化的制剂,这提出了一个重要的问题,即不同的GSE样品是否具有可比的活性,并在给定的生物系统上触发相同的作用机理。因此,很容易推测从不同品种获得的GSE可以发挥不同的抗癌作用。本研究的重点是确定从三种不同来源获得的GSE对人结肠癌细胞系Caco-2的选择性生物学功效。无论其来源如何,高剂量的GSE都会对Caco-2细胞的生长产生明显的抑制作用。而且,凋亡通过胱天蛋白酶依赖性和胱天蛋白酶非依赖性机制增强,导致早期凋亡诱导因子释放,并且进一步导致胱天蛋白酶7和3活性的急剧增加。但是,当用低和中等GSE浓度(25和50μg / ml)处理癌细胞时,三种葡萄来源引起的凋亡率明显不同。

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