Induction of apoptosis by 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol from Isaria japonica Yasuda through intracellular reactive oxygen species formation and caspase-3 activation in human leukemia HL-60 cells

Recently we have reported that the trichothecene mycotoxin 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol (AETD) from the fruiting bodies of Isaria japonica Yasuda is a potent inducer of apoptosis in human promyelocytic HL-60 cells. The present study aims to characterize the molecular events leadin...

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Bibliographic Details
Published in:Toxicology in vitro 2003-02, Vol.17 (1), p.49-57
Main Authors: Pae, H.O, Oh, G.S, Choi, B.M, Seo, E.A, Oh, H, Shin, M.K, Kim, T.H, Kwon, T.O, Chung, H.T
Format: Article
Language:English
Subjects:
4-Acetyl-12,13-epoxyl-9-trichothecene-3,15-diol
Apoptosis
Apoptosis - drug effects
Ascomycota - chemistry
Biological and medical sciences
Caspase 3
Caspases - pharmacology
Dose-Response Relationship, Drug
General pharmacology
Glutathione - metabolism
HL-60 Cells
Humans
Isaria japonica Yasuda
Medical sciences
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Reactive oxygen species
Reactive Oxygen Species - adverse effects
Trichothecene
Trichothecenes - pharmacology
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Summary:Recently we have reported that the trichothecene mycotoxin 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol (AETD) from the fruiting bodies of Isaria japonica Yasuda is a potent inducer of apoptosis in human promyelocytic HL-60 cells. The present study aims to characterize the molecular events leading to AETD-induced apoptosis in HL-60 cells. The percentage of apoptotic cells (annexin-V-positive cell population) increased dose- and time-dependently after AETD exposure. Apoptosis of HL-60 cells by AETD was associated with the formation of intracellular reactive oxygen species (ROS), the depletion of intracellular glutathione (GSH) and the activation of caspase-3. Pretreating the cells with the antioxidant N-acetyl- l-cystein (NAC) and the caspase-3 inhibitor Z-DEVD-fmk abrogated AETD-induced apoptosis and caspase-3 activation. NAC blocked intracellular ROS formation and GSH depletion, but Z-DEVD-fmk did not. These results indicate that AETD induces apoptosis in HL-60 cells by causing intracellular ROS formation and GSH depletion followed by the downstream event of caspase-3 activation.
ISSN:0887-2333
1879-3177
DOI:10.1016/S0887-2333(02)00097-8