Interferon-alpha suppresses proliferation of chronic myelogenous leukemia cells K562 by extending cell cycle S-phase without inducing apoptosis.
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.
Grebenová
Dana
D
Department of Cellular Biochemistry, Institute of Hematology and Blood Transfusion, 128 20, Prague-2, Czech Republic
Kuzelová
Katerina
K
Fuchs
Ota
O
Halada
Petr
P
Havlícek
Vladimír
V
Marinov
Iuri
I
Hrkal
Zbynĕk
Z
D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D020014:K562 Cells / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D040901:Proteomics; D016196:S Phase / Q000187:drug effects*; D014452:Ubiquitins / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D016898:Interferon-alpha; D014452:Ubiquitins; C074034:ISG15 protein, human; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl