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- Title
Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells.
- Authors
Liu, Feng-Ting; Kelsey, Stephen M.; Newland, Adrian C.; Jia, Li
- Abstract
The anthracycline antibiotic idarubicin (IDA) induces double-stranded DNA breaks, the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic cells. It is unclear whether the generation of ROS is associated with the apoptotic process. Using the T-lymphoblastic leukaemic CEM cell line, we found that IDA-induced DNA breaks were correlated with final cell death. The reduction in mitochondrial membrane potential (ΔΨm) and the generation of ROS occurred simultaneously with IDA-induced activation of caspase-9 and caspase-3. Inhibition of caspases by a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) completely blocked IDA-induced reduction of ΔΨm, apoptosis and final cell death. Interestingly, ROS generation was significantly enhanced by Z-VAD-fmk. ROS generation was neither caspase dependent nor part of the apoptotic process. IDA-mediated reduction in ΔΨm is caspase dependent and is not a consequence of the generation of ROS. These results indicate that IDA-induced generation of ROS and apoptosis are separate events. Inhibition of caspases facilitates IDA-mediated generation of ROS.
- Subjects
ACTIVE oxygen in the body; APOPTOSIS; LEUKEMIA; DNA damage
- Publication
British Journal of Haematology, 2001, Vol 115, Issue 4, p817
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2001.03216.x