Document Detail


Involvement of the Mitochondrion-dependent and the Endoplasmic Reticulum Stress-signaling Pathways in Isoliquiritigenin-induced Apoptosis of HeLa Cell.
MedLine Citation:
PMID:  23534467     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVE: Isoliquiritigenin (ISL), a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.
METHODS: Cell viability was evaluated using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit. The intracellular ROS levels were assessed using a 2, 7-dichlorofluorescein probe assay. The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5, 5', 6, 6'-tetra-chloro-1, 1', 3, 3'-tetraethyl-imidacarbocyanine iodide (JC-1). The degradation of poly-ADP-ribose polymerase (PARP) protein, the phosphorylation of PKR-like ER kinase (PERK), the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α), the expression of the 78 kD glucose-regulated protein (GRP 78), and the activation of caspase-12 were analyzed via western blot analysis.
RESULTS: ISL significantly inhibited the proliferation, the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner. Moreover, ISL induced mitochondrial dysfunction, caspase activation, and PARP cleavage, which displayed features of mitochondria dependent on apoptotic signals. Besides, exposure of HeLa cells to ISL triggered endoplasmic reticulum (ER) stress, as indicated by the increase in p-eIF2α and GRP78 expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.
CONCLUSION: The findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.
Authors:
Xuan Yuan; Bo Zhang; Lu Gan; Zhen Hua Wang; Ba Cui Yu; Liang Liang Liu; Qiu Sheng Zheng; Zhi Ping Wang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biomedical and environmental sciences : BES     Volume:  26     ISSN:  0895-3988     ISO Abbreviation:  Biomed. Environ. Sci.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8909524     Medline TA:  Biomed Environ Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  268-76     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
Affiliation:
Lanzhou University Second Hospital, Lanzhou University, Lanzhou 730000, Gansu, China.
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