Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells.
Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells.
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DOI：
10.1039/c5fo00388a
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发表时间：
2015-08
期刊：
影响因子：
6.1
通讯作者：
Tian-Tian Zhang-Tian;Li Yang-;Jian-Guo Jiang
中科院分区：
文献类型：
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作者：
Tian-Tian Zhang-Tian;Li Yang-;Jian-Guo Jiang
采用MTT法、流式细胞术、实时荧光定量PCR和Western blotting等方法研究托宁宁甲素对人肝癌细胞株HepG-2的抑制作用。结果表明，Thonningianin A可通过诱导HepG-2细胞凋亡，抑制HepG-2细胞增殖，表现为亚G1期细胞数增加、DNA断裂和活性氧含量增加。半胱天冬酶-9的激活和随后的半胱天冬酶-3的激活表明，Thonningianin A诱导的细胞凋亡是半胱天冬酶依赖性的。Thonningianin A还可使HepG-2细胞线粒体膜电位（Δ Δ m）降低，并下调Bcl-xL mRNA的表达。Thonningianin A通过改变cyclin D1和CDK 4 mRNA表达水平诱导细胞周期阻滞。Western blotting结果显示，Thonningianin A显著下调NF-κ B-B细胞存活通路，同时沿着上调磷酸化P38的表达水平和下调磷酸化ERK的表达水平。Thonningianin A的抗肿瘤活性通过DNA断裂和细胞周期阻滞的特征模式得到证实，提示ThA是天然植物食品中有效的抗肿瘤成分，值得进一步研究。
The anti-cancer activities of Thonningianin A on the HepG-2 human hepatocellular carcinoma cell line were evaluated by MTT assay, flow cytometry, quantitative real-time PCR and western blotting. Results showed that Thonningianin A effectively inhibited the proliferation of HepG-2 cells by inducing apoptosis, as evidenced by increase in the sub-G1 cell population, DNA fragmentation, and increase in the content of reactive oxygen species. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that Thonningianin A-induced apoptosis is caspase-dependent. Thonningianin A also disrupted the mitochondrial membrane potential (Δψm) and down-regulated the Bcl-xL mRNA expression in HepG-2 cells. Thonningianin A induced cell cycle arrest by changing the cyclin D1 and CDK4 mRNA expression levels. Moreover, western blotting showed that Thonningianin A significantly down-regulated the NF-kappa-B cell survival pathway, along with up-regulation of the expression level of phosphorylated P38 and down-regulation of the expression level of phosphorylated ERK. The anti-cancer activity of Thonningianin A was confirmed by the characteristic patterns of DNA fragmentation and cell cycle arrest, suggesting that Th A is an effective antitumor ingredient in natural plant foods, and is worthy of further study.