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Apoptotic cell death induced by Z-Ligustilidein human ovarian cancer cells and role of NRF2
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-09-20 , DOI: 10.1016/j.fct.2018.09.041
Fangfang Lang , Jinfeng Qu , Haiqin Yin , Lanyu Li , Yuanyuan Zhi , Yanping Liu , Zhenghui Fang , Enkui Hao

Z-Ligustilide is the most potent bioactive component of Angelica sinensis, which is widely used in Chinese traditional medicine. Z-Ligustilide selectively affected ovarian cancer cell survival in a dose dependent manner. Z-Ligustilide induced apoptotic cell death was determined by flow cytometry. We also demonstrated that apoptotic cell death was triggered by Z-Ligustilideinduced oxidative stress and mitochondria played an active role. Mitochondrial polarization was reduced by Z-Ligustilidewhereas mitochondrial superoxide formation was increased. NRF2 was induced by Z-Ligustilide in OVCAR-3 cells at epigenetic level and its downstream antioxidant defense genesHeme oxygenase-1,NAD(P)H Quinone Dehydrogenase 1, UDP Glucuronosyltransferase Family 1 Member A1and Glutamate-Cysteine Ligase. NRF2 knockdown by siRNA resulted increased cell death by Z-Ligustilide in ovarian cancer cells. Our result demonstrated the pro-survival role of NRF2 in Z-Ligustilide induced ovarian cancer cell death.



中文翻译:

Z-川gust嗪诱导人卵巢癌细胞凋亡及NRF2的作用

Z-Li本内酯是当归中最有效的生物活性成分,在中药中广泛使用。Z-Li本内酯以剂量依赖性方式选择性地影响卵巢癌细胞的存活。通过流式细胞术确定Z-Li本内酯诱导的凋亡细胞死亡。我们还证明了Z-Li啶内酯诱导的氧化应激触发了凋亡细胞的死亡,线粒体发挥了积极的作用。Z-川gust嗪减少了线粒体的极化,而线粒体超氧化物的形成增加了。Z-Li啶内酯在表皮遗传水平上在OVCAR-3细胞及其下游抗氧化防御基因中诱导了NRF2血红素加氧酶-1,NAD(P)H醌脱氢酶1,UDP葡萄糖醛酸转移酶家族1成员A1和谷氨酸半胱氨酸连接酶。siRNA对NRF2的抑制作用导致Z-Ligustilide在卵巢癌细胞中的细胞死亡增加。我们的结果证明了NRF2在Z-Li古丁内酯诱导的卵巢癌细胞死亡中的生存作用。

更新日期:2018-09-20
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