title: Etoposide-induced apoptosis is not associated with the fas pathway in acute myeloblastic leukemia cells.
abstract: Two subclones of the OCI/AML-2 cell line, etoposide-sensitive (ES) and etoposide-resistant (ER), established by the authors, were used as models. We investigated whether the Fas pathway is involved in etoposide-induced apoptosis in acute myeloblastic leukemia (AML). Both of the studied subclones expressed the Fas receptor (FasR), but only the ER cell line expressed the Fas ligand (FasL). Etoposide caused an increase in the mean fluorescence intensity of FasR in both subclones, and an induction of FasL in the ES subclone. However, no change in the numbers of apoptotic cells induced by etoposide was observed when FasR was blocked by an antagonist anti-Fas antibody, nor was an agonist anti-Fas antibody alone cytotoxic to the subclones or enhanced the cytotoxic effect of etoposide. The Fas-resistant phenotype of the AML cells was converted to a Fas-sensitive one by cycloheximide (CHX) suggesting the presence of an inhibitory protein of the Fas pathway in the cells. In etoposide-induced apoptosis, the effect of CHX was different, apoptosis-preventing. In conclusion, etoposide-induced apoptosis is not mediated by the Fas pathway in AML.
authors.affiliation: Department of Internal Medicine, University of Oulu, Kajaanintie 50, FIN-90220, Oulu, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Siitonen
authors.forename: P
authors.initials: P
authors.lastname: Mäntymaa
authors.forename: M
authors.initials: M
authors.lastname: Säily
authors.forename: E
authors.initials: E
authors.lastname: Savolainen
authors.forename: P
authors.initials: P
authors.lastname: Koistinen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology*; D053222:Fas Ligand Protein; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000032:analysis / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D005047:Etoposide; D003513:Cycloheximide