title: Oxymatrine triggers apoptosis by regulating Bcl-2 family proteins and activating caspase-3/caspase-9 pathway in human leukemia HL-60 cells.
abstract: 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.
authors.affiliation: Department of Geriatrics, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Yao
authors.forename: Huifang
authors.initials: H
authors.lastname: Ding
authors.forename: Renan
authors.initials: R
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology*; D053181:Caspase 8 / Q000502:physiology; D053453:Caspase 9 / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011807:Quinolizines / Q000494:pharmacology*; D015398:Signal Transduction; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D011065:Poly(ADP-ribose) Polymerases; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines; C505407:CASP3 protein, human; C506433:CASP9 protein, human