Arsenic trioxide-induced apoptosis is independent of CD95 in lymphatic cell lines.
The potency of arsenic trioxide (As2O3) as chemotherapeutic agent is under investigation in various clinical trials. As2O3 was shown to be a potent inductor of apoptosis, and several publications describe the involvement of caspases, reduction of mitochondrial membrane potential and modulation of intracellular glutathione level. However, little is known about the involvement of membrane bound cell death receptors. We investigated the role of CD95 and CD95L in As2O3 mediated apoptosis in various lympho-haematopoietic cell lines. Basal CD95-expression did not correlate with sensitivity to As2O3 and incubation with As2O3 did not alter CD95-expression. We therefore chose two CD95 positive cell lines (CCRF-CEM and Jurkat) to analyse a potential activation of this pathway. We were able to induce apoptosis in these CD95 positive cell lines with activating anti-CD95 antibodies and could block induction of apoptosis by inhibitory anti-CD95 antibodies. In contrast we were not able to block As2O3-induced apoptosis by inhibitory anti-CD95 antibodies. We could block additive effects of arsenic trioxide and an apoptosis-inducing anti-CD95 antibody against CD95 to levels of arsenic trioxide alone using an inhibitory anti-CD95 antibody. Thus, our data provide no evidence for a role of the CD95L/CD95 pathway in As2O3-induced apoptosis.
Rojewski
Markus Thomas
MT
Universitäts-klinikum Ulm, Abteilung Transfusionsmedizin und Institut für Klinische Transfusionsmedizin und Immungenetik gGmbH, Heimholtzstrasse 10, 89081 Ulm, Germany. markus.rojewski@medizin.uni-ulm.de
Körper
Sixten
S
Thiel
Eckhard
E
Schrezenmeier
Hubert
H
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D019169:Jurkat Cells; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D010087:Oxides / Q000494:pharmacology*; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D015703:Antigens, CD; D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D019014:fas Receptor; D018698:Glutamic Acid; D000077237:Arsenic Trioxide