title: The role of mitochondrial targeting in arsenic trioxide-induced apoptosis in myeloid cell lines.
abstract: Data regarding the role of mitochondria in arsenic trioxide (As2O3)-induced apoptosis are controversial. We investigated the contribution of caspases and mitochondrial depolarization to As2O3-induced apoptosis in the myeloid cell lines NB-4, HL-60 and U-937. Caspase inhibition reduced the amount of cells with As2O3 (20 micromol/l)-induced mitochondrial depolarization by about 50% in all cell lines. As2O3 also induced dose-dependent phosphatidylserine exposure in cells without depolarized mitochondria. We conclude that caspase activation is of similar importance in As2O3-induced apoptosis in myeloid cell lines as direct mitochondrial targeting and mitochondria are not necessary for caspase activation downstream of mitochondria.
authors.affiliation: Institut für klinische Transfusionsmedizin und Immungenetik Ulm und Abtl. Transfusionsmedizin der Universität Ulm, Helmholtz-Strasse 10, D-89081 Ulm, Germany. sixten.koerper@medizin.uni-ulm.de
authors.forename: Sixten
authors.initials: S
authors.lastname: Körper
authors.forename: Florian
authors.initials: F
authors.lastname: Nolte
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Markus T
authors.initials: MT
authors.lastname: Rojewski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D061945:Caspase Inhibitors; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000201:enzymology; D010087:Oxides / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D061945:Caspase Inhibitors; D010087:Oxides; D000077237:Arsenic Trioxide