1. The cytotoxic macrolide FD-891 induces caspase-8-dependent mitochondrial release of cytochrome c and subsequent apoptosis in human leukemia Jurkat cells
- Author
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Susumu Inaba, Takeo Usui, Tadashi Eguchi, Atsushi Motegi, Kazuo Nagai, Takao Kataoka, and Kazutoshi Mizoue
- Subjects
Pharmacology ,Caspase 8 ,Antibiotics, Antineoplastic ,biology ,Cytochrome c ,Cytochromes c ,Apoptosis ,Jurkat cells ,Mitochondrial apoptosis-induced channel ,Molecular biology ,Caspase 9 ,Mitochondria ,Cell biology ,Jurkat Cells ,Cell culture ,Drug Discovery ,biology.protein ,Humans ,Cytotoxic T cell ,Macrolides ,Apoptosome ,Cell Proliferation - 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-x(L) or the caspase-8 modulator c-FLIP(L) 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.
- Published
- 2009