國家衛生研究院 NHRI:Item 3990099045/2246
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    題名: Molecular mechanisms of ginsenoside Rh2-mediated G(1) growth arrest and apoptosis in human lung adenocarcinoma A549 cells
    作者: Cheng, CC;Yang, SM;Huang, CY;Chen, JC;Chang, WM;Hsu, SL
    貢獻者: Division of Molecular and Genomic Medicine
    摘要: Ginsenoside Rh2 (Rh2), a purified ginseng saponin, has been shown to have antiproliferative effects in certain cancer cell types. However, the molecular mechanisms of Rh2 on cell growth and death have not been fully clarified. In this study, the antiproliferative effect of Rh2 in human lung adenocarcinoma A549 cells was investigated. Treatment of A549 cells with 30 mu g/ml Rh2 resulted in G(1) phase arrest, followed by progression to apoptosis. This Rh2-mediated G(1) arrest was accompanied by downregulation of the protein levels and kinase activities of cyclin-D1, cyclin-E and Cdk6, and the upregulation of pRb2/p130. In addition, Rh2-induced apoptosis was confirmed by TUNEL assay and DNA fragmentation analysis. Administration of Rh2 caused an increase in the expression levels of TRAIL-RI (DR4) death receptor but did not alter the levels of other death receptors or Bcl-2 family molecules. Furthermore, the Rh2-induced apoptosis was significantly inhibited by DR4:Fc fusion protein, which inhibits TRAIL-DR4-mediated apoptosis. In addition, caspase-2, caspase-3 and caspase-8 were highly activated upon Rh2 treatment. Inhibitors of caspase-2, caspase-3 and caspase-8 markedly prevented the cell death induced by Rh2. Inhibitor of caspase-8 significantly inhibited the activation of caspase-2, caspase-3 and caspase-8. These observations indicate that multiple G(1)-related cell cycle regulatory proteins are regulated by Rh2 and contribute to Rh2-induced G(1) growth arrest. The increase in the expression level of DR4 death receptor may play a critical role in the initiation of Rh2-triggered apoptosis, and the activation of the caspase-8/caspase-3 cascade acts as the executioner of the Rh2-induced death process.
    關鍵詞: Oncology;Pharmacology & Pharmacy
    日期: 2005-06
    關聯: Cancer Chemotherapy and Pharmacology. 2005 Jun;55(6):531-540.
    Link to: http://dx.doi.org/10.1007/s00280-004-0919-6
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0344-5704&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000228728400003
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=18744403057
    顯示於類別:[黃奇英(1998-2005)] 期刊論文

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