Strophalloside induces apoptosis of SGC-7901 cells through the mitochondrion-dependent caspase-3 pathway.

Strophalloside induces apoptosis of SGC-7901 cells through the mitochondrion-dependent caspase-3 pathway.
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球冬甙通过线粒体依赖性 Caspase-3 途径诱导 SGC-7901 细胞凋亡

DOI:
10.3390/molecules20045714
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发表时间:
2015-03-31
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Huang FY
Huang FY
中科院分区:
其他
文献类型:
--
作者:
Zhang XJ;Mei WL;Tan GH;Wang CC;Zhou SL;Huang FR;Chen B;Dai HF;Huang FY

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具有特殊化学结构的Cardenolide在临床试验中被认为是有效的抗癌药物。白花蛇舌草苷是我们最近从海南毒蛾中国中分离得到的一种万寿菊内酯。本研究的目的是探讨白花蛇舌草皂苷可能的抗癌作用及其分子机制。采用四甲基偶氮唑蓝比色法检测不同浓度的千金藤皂苷作用于胃癌SGC-7901细胞不同时间后的细胞存活率,用Transwell小室实验检测肿瘤细胞的运动和侵袭能力。Annexin V-FITC/PI和Hoechst染色检测细胞凋亡率。用JC-1试剂盒检测线粒体跨膜电位的变化。免疫印迹法检测促凋亡蛋白细胞色素c、caspase-3、caspase-9的表达。结果表明,白花蛇舌草皂苷具有时间和剂量依赖性地降低细胞存活率、抑制细胞生长、抑制细胞迁移和侵袭的作用。线粒体膜电位下降,胞浆内细胞色素c浓度升高,caspase-3和caspase-9被裂解为激活状态,提示细胞色素c从线粒体释放到细胞质,最终激活caspase依赖的细胞凋亡途径。我们的结果表明,白花蛇舌草苷是一种潜在的抗癌药物。
Cardenolides with special chemical structures have been considered as effective anti-cancer drugs in clinic trials. Strophalloside is a cardenolide we recently isolated from Antiaris toxicaria obtained from Hainan, China. The aim of this study was to investigate the possible anticancer effects induced by strophalloside and the underlying molecular mechanism. Gastric carcinoma SGC-7901 cells were treated with strophalloside at various concentrations for different times, and resulting cell viability was determined by the MTT assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Apoptosis were measured by Annexin V-FITC/PI and Hoechst staining. The changes of mitochondrial transmembrane potential were examined by a JC-1 kit. The expressions of pro-apoptotic protein cytochrome c, caspase-3 and caspase-9 were detected by western blotting analysis. The results showed that strophalloside was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion in a time- and dose-dependent manner. Mitochondrial membrane potential declined and the concentration of cytochrome c increased in cytoplasm and caspase-3 and caspase-9 were cleaved into activated states, suggesting that cytochrome c was released from the mitochondrion to cytoplasm and finally activated the caspase-dependent apoptosis pathway. Our results indicate that strophalloside is a potential anticancer drug.
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