Apoptotic cell death induced by Z-Ligustilidein human ovarian cancer cells and role of NRF2

作者：Lang, Fangfang; Qu, Jinfeng; Yin, Haiqin; Li, Lanyu; Zhi, Yuanyuan; Liu, Yanping; Fang, Zhenghui; Hao, Enkui^*

来源：Food and Chemical Toxicology, 2018, 121: 631-638.

DOI：10.1016/j.fct.2018.09.041

• Ovarian cancer
• Ligustilide
• Mitochondria
• Apoptosis
• Oxidative stress

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 mitochondria] 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 A1 and 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.

• 出版日期2018-11
• 单位济南市中心医院; 山东大学; 山东省千佛山医院