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

• Published in: Tumor biology Vol. 35; no. 6; pp. 5409 - 5415
• Main Authors: Liu, Jun, Yao, Yazhou, Ding, Huifang, Chen, Renan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2014; Springer Nature B.V
• Subjects: Alkaloids - pharmacology; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cancer Research; Caspase 3 - physiology; Caspase 8 - physiology; Caspase 9 - physiology; Cell Cycle Checkpoints - drug effects; Cellular biology; Herbal medicine; HL-60 Cells; Humans; Leukemia; Poly(ADP-ribose) Polymerases - physiology; Protein expression; Proto-Oncogene Proteins c-bcl-2 - physiology; Quinolizines - pharmacology; Research Article; Signal Transduction; Caspase; HL-60; Bax/Bcl-2; Oxymatrine; Apoptosis
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-1705-7

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 G 2 /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.