Oxymatrine triggers apoptosis by regulating Bcl-2 family proteins and activating caspase-3/caspase-9 pathway in human leukemia HL-60 cells

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• 作者：Jun Liu (1)
  Yazhou Yao (2)
  Huifang Ding (3)
  Renan Chen (4)
  
• 关键词：Oxymatrine ; Apoptosis ; HL ; 60 ; Caspase ; Bax/Bcl ; 2
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：35
• 期：6
• 页码：5409-5415
• 全文大小：
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• 作者单位：Jun Liu (1)
  Yazhou Yao (2)
  Huifang Ding (3)
  Renan Chen (4)
  
  1. Department of Geriatrics, Tangdu Hospital, the Fourth Military Medical University, Xi鈥檃n, 710038, China
  2. Department of Haematologic and Rheumatism, Baoji Central Hospital, BaoJi, 721008, China
  3. Department of Haematology, Shengli Oilfield Central Hospital, Dongying, 257034, China
  4. Department of Haematology, Tangdu Hospital, the Fourth Military Medical University, Xi鈥檃n, 710038, China
  
• ISSN：1423-0380

文摘

With the objective of identifying promising antitumor agents for human leukemia, we carried out to determine the anticancer ability of oxymatrine on the human leukemia HL-60 cell line. In vitro experiments demonstrated that oxymatrine reduced the proliferation of HL-60 cells in a dose- and time-dependent manner via the induction of apoptosis and cell cycle arrest at G2/M and S phases. The proteins involved in oxymatrine-induced apoptosis in HL-60 cells were also examined using Western blot. The increase in apoptosis upon treatment with oxymatrine was correlated with downregulation of anti-apoptotic Bcl-2 expression and upregulation of pro-apoptotic Bax expression. Furthermore, oxymatrine induced the activation of caspase-3 and caspase-9 and the cleavage of poly(ADP-ribose) polymerase (PARP) in HL-60 cells. In addition, pretreatment with a specific caspase-3 (Z-DEVD-FMK) or caspase-9 (Z-LEHD-FMK) inhibitor significantly neutralized the pro-apoptotic activity of oxymatrine in HL-60 cells, demonstrating the important role of caspase-3 and caspase-9 in this process. Taken together, these results indicated that oxymatrine-induced apoptosis may occur through the activation of the caspase-9/caspase-3-mediated intrinsic pathway. Therefore, oxymatrine may be a potential candidate for the treatment of human leukemia.