Abstract
The 16-membered macrolide FD-891 exerts cytotoxicity toward several cancer cell lines. In this study, we showed that FD-891 induces apoptosis in various human cancer cell lines. Human leukemia Jurkat cells were highly sensitive to FD-891, exhibiting caspase activation and mitochondrial release of cytochrome c into the cytosol at early time points after exposure to FD-891. By contrast, Jurkat cells deficient in caspase-8 were resistant to FD-891-induced apoptosis and manifested little induction of cytochrome c release as well as caspase-9 processing. Consistent with these results, the overexpression of the Bcl-2 family member Bcl-xL or the caspase-8 modulator c-FLIPL markedly prevented FD-891-induced apoptosis. These results clearly demonstrate that FD-891 triggers caspase-8-dependent mitochondrial release of cytochrome c and subsequent apoptosis in Jurkat cells.
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This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
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Inaba, S., Eguchi, T., Motegi, A. et al. The cytotoxic macrolide FD-891 induces caspase-8-dependent mitochondrial release of cytochrome c and subsequent apoptosis in human leukemia Jurkat cells. J Antibiot 62, 507–512 (2009). https://doi.org/10.1038/ja.2009.62
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DOI: https://doi.org/10.1038/ja.2009.62
