title: Fludarabine nucleoside modulates nuclear "survival and death" proteins in resistant chronic lymphocytic leukemia cells.
abstract: The nuclear mechanisms by which fludarabine nucleoside (F-ara-A) induces apoptosis have been investigated in human MEC1 cells derived from B-cell chronic lymphocytic leukemia. Upon treatment of cells with F-ara-A (100 μM, 72 hours), 15 nuclear proteins changed in abundance by more than 2-fold. Nuclear proteins up-regulated included calmodulin (4.3-fold), prohibitin (3.9-fold), β-actin variant (3.7-fold), and structure-specific recognition protein 1 (3.7-fold); those down-regulated included 60S ribosomal protein P2B (0.12-fold), fumarate hydratase (0.19-fold), splicing factor arginine/serine-rich 3 (0.35-fold), and replication protein A2 (0.42-fold). These changes in the levels of specific proteins promote survival or apoptosis; because the end result is apoptosis of MEC1 cells, apoptotic effects predominate.
authors: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors: Silke
authors: S
authors: Henrich
authors: Swetlana
authors: S
authors: Mactier
authors: Giles
authors: G
authors: Best
authors: Stephen P
authors: SP
authors: Mulligan
authors: Ben
authors: B
authors: Crossett
authors: Richard Ian
authors: RI
authors: Christopherson
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D009705:Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D009687:Nuclear Proteins; D009705:Nucleosides; D014740:Vidarabine; C024352:fludarabine