RRC ID 73028
Author Miura K, Aminova L, Murayama Y.
Title Fusarenon-X induced apoptosis in HL-60 cells depends on caspase activation and cytochrome c release.
Journal Toxicology
Abstract Fusarenon-X (FX), a trichothecene mycotoxin, is well known to be cytotoxic to mammalian cells. Our previous study revealed that FX induced apoptosis in mouse thymocytes both in vivo and in vitro. We investigated the mode of apoptosis induced by FX using HL-60 cell culture. When FX at a final concentration of 0.5 microg/ml was added, cell degradation was observed 5 h after exposure, and most of the cells had fallen into apoptosis 24 h after exposure. DNA fragmentation into 180-bp multimers was observed 5 h after exposure, and its dose-dependency was clear in the cells treated with 0.1 microg/ml and higher doses. The percentage of apoptotic cells (sub-G(0) population) increased dose- and time-dependently after exposure, when analyzed using flow cytometry. The activities of caspase-3, -8, and -9 were elevated within 2 h by exposure to FX. DNA fragmentation and an increase in the apoptotic population were abrogated by pre-treating the cells with broad-spectrum caspase inhibitors Z-VAD-fmk or Z-Asp-CH(2)-DCB. Cytochrome c release from mitochondria to cytoplasm was observed clearly, and this release occurred caspase-independently. These findings suggest that FX induces apoptosis in HL-60 cells by stimulating cytochrome c release followed by its downstream events including the activation of multiple caspases.
Volume 172(2)
Pages 103-12
Published 2002-3-20
DOI 10.1016/s0300-483x(01)00586-8
PII S0300483X01005868
PMID 11882350
MeSH Apoptosis / drug effects* Caspase Inhibitors Caspases / metabolism* Cell Division / drug effects Cytochrome c Group / metabolism* DNA Fragmentation / drug effects Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Flow Cytometry HL-60 Cells Humans Mitochondria / drug effects Mitochondria / metabolism Mycotoxins / toxicity* Trichothecenes / toxicity*
IF 4.099
Human and Animal Cells HL60(RCB0041)