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Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma cells via the ROS-mediated MAPK/AKT/NF-κB signaling pathway

甘草苷通过 ROS 介导的 MAPK/AKT/NF-κ b 信号通路抑制 HepG2 肝癌细胞增殖并诱导其凋亡

  • 影响因子:2.08
  • DOI:10.1007/s00210-019-01763-7
  • 作者列表:"Wang, Jia-Ru","Li, Tian-Zhu","Wang, Cheng","Li, Shu-Mei","Luo, Ying-Hua","Piao, Xian-Ji","Feng, Yu-Chao","Zhang, Yi","Xu, Wan-Ting","Zhang, Yu","Zhang, Tong","Wang, Shi-Nong","Xue, Hui","Wang, Hong-Xing","Cao, Long-Kui","Jin, Cheng-Hao
  • 发表时间:2020-01-20
Abstract

Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl- l -cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.

摘要

甘草苷 (LIQ) 是甘草的主要成分,具有多种药理活性。本研究旨在探讨 LIQ 在肝细胞癌 (HCC) 细胞中的潜在抗癌作用及其潜在的分子机制。LIQ 通过降低线粒体膜电位和调节细胞色素 c 、 Bcl-2 和 cle-PARP 家族蛋白,显著降低 HepG2 细胞的活力并诱导 cle-caspase-3 凋亡。细胞周期分析和 western blot 分析发现,LIQ 通过增加 p21 的表达和降低 p27 、 cyclin B 和 CDK1/2 的水平诱导 G2/M 期阻滞。流式细胞术和 western blot 分析也提示 LIQ 促进 HepG2 细胞内 ROS 的积累,上调 p38 激酶的磷酸化表达水平, c-6月 N 末端激酶 (JNK) 和 NF-κ b 抑制剂 (i κ b-α); 细胞外信号调节激酶 (ERK) 的磷酸化水平, 蛋白激酶 B (AKT),信号转导子转录激活子 3 (STAT3) 和核因子 κ B (NF-κ B) 表达下调。然而,这些作用被 N-乙酰-l-半胱氨酸 (NAC) 、 MAPK 和 AKT 抑制剂逆转。研究结果表明,LIQ 通过 ROS 介导的 MAPK/AKT/NF-κ b 信号通路诱导 HepG2 细胞周期阻滞和凋亡, LIQ 有望成为治疗肝癌的潜在药物。

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翻译标题与摘要 下载文献
影响因子:3.87
发表时间:2020-02-01
DOI:10.1111/liv.14321
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

翻译标题与摘要 下载文献
影响因子:2.57
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DOI:10.1111/eci.13198
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