Interferon-alpha suppresses proliferation of chronic myelogenous leukemia cells K562 by extending cell cycle S-phase without inducing apoptosis

Blood Cells Mol Dis. 2004 Jan-Feb;32(1):262-9. doi: 10.1016/j.bcmd.2003.10.008.

Abstract

We examined the effects of interferon-alpha (IFN-alpha) treatment on the growth, cell cycle, proliferation, and apoptotic parameters as well as adhesive properties and proteome of chronic myelogenous leukemia (CML)-derived K562 cells. IFN-alpha treatment (200 to 600 U/ml, 24 to 72 h) suppressed growth and caused accumulation of K562 cells in the S-phase of cell cycle (increase in S-phase cells by up to 52% in comparison with the untreated controls) at the expenses of cells in G1-phase. No transition of cells to G0-phase occurred as followed from Ki-67 protein determination. Although the level of chimeric gene product, BCR-ABL mRNA coding for BCR-ABL protein with anti-apoptotic properties, decreased by 30%, apoptosis was not triggered as judged from Annexin-V, APO2.7, and TUNEL assays. Adhesion of K562 cells to fibronectin-coated surfaces increased by up to 52% as determined by calcein assay. The proteomic analysis (2-D electrophoresis in combination with mass spectrometry, MALDI-MS) revealed a single protein, ubiquitine cross-reactive protein (UBCR), whose level markedly increased due to IFN-alpha treatment. The ubiquitination-like directed degradation processes may thus play a role in the mechanism of IFN-alpha antiproliferative effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Adhesion
  • Cell Division / drug effects
  • Cytokines / biosynthesis
  • Cytokines / drug effects
  • Fusion Proteins, bcr-abl
  • Humans
  • Interferon-alpha / pharmacology*
  • K562 Cells / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Protein-Tyrosine Kinases / analysis
  • Proteomics
  • S Phase / drug effects*
  • Ubiquitins / analogs & derivatives
  • Ubiquitins / biosynthesis
  • Ubiquitins / drug effects
  • Up-Regulation / drug effects

Substances

  • Cytokines
  • Interferon-alpha
  • Ubiquitins
  • ISG15 protein, human
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl