The cytotoxic macrolide FD-891 induces caspase-8-dependent mitochondrial release of cytochrome c and subsequent apoptosis in human leukemia Jurkat cells.
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.
Inaba
Susumu
S
Center for Biological Resources and Informatics, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama, Japan.
Eguchi
Tadashi
T
Motegi
Atsushi
A
Mizoue
Kazutoshi
K
Usui
Takeo
T
Nagai
Kazuo
K
Kataoka
Takao
T
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D018942:Macrolides / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D018942:Macrolides; C091118:FD 891; D045304:Cytochromes c; D053181:Caspase 8; D053453:Caspase 9