title: p53 and redox state in etoposide-induced acute myeloblastic leukemia cell death.
abstract: We investigated whether p53, being a redox-sensitive protein, has a role in the responsiveness of AML cells to etoposide. Two subclones of the OCI/AML-2 cell line, the etoposide-sensitive (ES) and the etoposide-resistant (ER), were used as models. Sensitivity to etoposide was measured by trypan blue and annexin V assays. Etoposide-induced peroxide formation was associated with the induction of cell death. Evident expression of mutated p53 was observed in both subclones in basal growth conditions as analysed by Western blotting and flow cytometry. After etoposide exposure for up to 24 hours, some nuclear accumulation of p53 was observed in the ER subclone, as analysed by Western blotting. The conformation of p53, however, was not changed from mutated toward wild-type during exposure in either of the subclones as analysed by flow cytometry. In conclusion, etoposide-induced change in cellular redox state was associated with apoptosis, but was not a sufficient stimulus for p53 to make its conformation active. Thus, mutated p53 seems to have no role in etoposide-induced apoptosis.
authors.affiliation: Department of Internal Medicine, University of Oulu, Kajaanintie 50, FIN-90220 Oulu, Finland. pirjo.koistinen@ppshp.fi
authors.forename: P
authors.initials: P
authors.lastname: Koistinen
authors.forename: T
authors.initials: T
authors.lastname: Siitonen
authors.forename: P
authors.initials: P
authors.lastname: Mäntymaa
authors.forename: E R
authors.initials: ER
authors.lastname: Savolainen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010084:Oxidation-Reduction; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D011065:Poly(ADP-ribose) Polymerases