國家衛生研究院 NHRI:Item 3990099045/10994
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    题名: Glycyrrhizic acid induces human MDA-MB-231 breast cancer cell death and autophagy via the ROS-mitochondrial pathway
    作者: Lin, SC;Chu, PY;Liao, WT;Wu, MY;Tsui, KH;Lin, LT;Huang, CH;Chen, LL;Li, CJ
    贡献者: National Institute of Cancer Research
    摘要: Glycyrrhizic acid (GA), the main component of licorice root extracts, has been shown to suppress cell proliferation and induce apoptosis in various types of cancers. However, the molecular mechanism of its anticancer activity remains poorly understood and warrants further investigation. MDA-MB-231 cells were treated with various concentrations of GA and the cytotoxic effects of GA were determined using the CCK-8 assay. Apoptosis and cell cycle status were detected by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (m) were assessed using DCFDA, MitoSOX and JC-1 staining. Western blot analysis was used to quantify the expression of autophagyrelated proteins. In the present study, induction of autophagic cell death was observed in GA-treated MDA-MB-231 cells. Downregulation of p62- and beclin 1-associated proteins occurred after GA treatment, and, the conversion of LC3 and increased ROS without significant changes in caspase-associated proteins and intracellular responses were detected. Furthermore, loss of mitochondria and its membrane potential in cells demonstrated that mitochondria were involved in the GA-regulated MDA-MB-231 cell death. The addition of a pan-caspase inhibitor (z-VAD-fmk) did not suppress the GA-induced apoptotic effect, and GA-induced apoptosis was not accompanied by processing of procaspase-8, -9 and -3. However, GA triggered the translocation of the apoptosisinducing factor (AIF) from the mitochondria into the nucleus. In contrast, GA-induced LC3 conversion was significantly inhibited by 3 methlyadenine (3MA), an inhibitor of PI3K-regulated autophagy. Therefore, these results suggest that enhancement of both AIF- and LC3-dependent GA-derived ROS generation plays an important role in the inhibition of the growth of MDA-MB-231 human breast cancer cells.
    日期: 2018-02
    關聯: Oncology Reports. 2018 Feb;39(2):703-710.
    Link to: http://dx.doi.org/10.3892/or.2017.6123
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-335X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000422855800030
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85038382052
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