Antioxidant and Proapoptotic Activities of Sclerocarya birrea [(A. Rich.) Hochst.] Methanolic Root Extract on the Hepatocellular Carcinoma Cell Line HepG2

Antioxidant and Proapoptotic Activities of Sclerocarya birrea [(A. Rich.) Hochst.] Methanolic Root Extract on the Hepatocellular Carcinoma Cell Line HepG2
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DOI:
10.1155/2015/561589
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发表时间:
2015-01-01
影响因子:
--
通讯作者:
Milella, Luigi
Milella, Luigi
中科院分区:
生物学3区
文献类型:
--
作者:
Armentano, Maria Francesca;Bisaccia, Faustino;Milella, Luigi

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本研究的主要目的是在体外的抗氧化活性和S。birrea methanolic root extract(MRE).在四个测试的提取物中,用不同的溶剂,MRE表现出最高含量的多酚,类黄酮,单宁一起与超氧化物,一氧化氮,ABTS,β-胡萝卜素漂白试验测试的抗氧化活性。此外,MRE对肝癌细胞系HepG 2的细胞毒作用进行了评价。在这些细胞中,MRE处理诱导凋亡,并产生活性氧(ROS)的剂量依赖性的方式。用N-乙酰-L-半胱氨酸(NAC)预处理HepG 2细胞可阻止MRE促进的细胞毒性作用,表明氧化应激在MRE介导的细胞死亡中起关键作用。此外,我们发现,MRE处理诱导线粒体膜去极化和细胞色素c从线粒体释放到胞质溶胶。提示细胞凋亡是通过细胞凋亡依赖性途径发生的。有趣的是,与HepG 2细胞相比,MRE在正常人皮肤成纤维细胞中显示出明显较低的细胞毒性,与ROS的低增加相关。结果表明,S. Birrea能够选择性地增加癌细胞中的细胞内ROS水平,促进细胞死亡。
The main goal of this study was to characterize the in vitro antioxidant activity and the apoptotic potential of S. birrea methanolic root extract (MRE). Among four tested extracts, obtained with different solvents, MRE showed the highest content of polyphenols, flavonoids, and tannins together with antioxidant activities tested with superoxide, nitric oxide, ABTS, and beta-carotene bleaching assays. Moreover, the cytotoxic effect of MRE was evaluated on the hepatocarcinoma cell line HepG2. In these cells, MRE treatment induced apoptosis and generated reactive oxygen species (ROS) in dose-dependent manner. The cytotoxic effect promoted by MRE was prevented by pretreatment of HepG2 cells with N-acetyl-L-cysteine (NAC), suggesting that oxidative stress was pivotal in MRE mediated cell death. Moreover, we showed that the MRE treatment induced the mitochondrial membrane depolarization and the cytochrome c release from mitochondria into the cytosol. It suggests that the apoptosis occurred in a mitochondrial-dependent pathway. Interestingly, MRE showed a sensibly lower cytotoxicity, associated with a low increase of ROS, in normal human dermal fibroblasts compared to HepG2 cells. It is suggested that the methanolic root extract of S. Birrea is able to selectively increase intracellular ROS levels in cancer cells, promoting cell death.