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Macromolecular Changes in Nilotinib Resistant K562 Cells; an In vitro Study by Fourier Transform Infrared Spectroscopy.
MedLine Citation:
PMID:  22712605     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Nilotinib is a second generation tyrosine kinase inhibitor which is used in both first and second line treatment of chronic myeloid leukemia (CML). In the present work, the effects of nilotinib resistance on K562 cells were investigated at the molecular level using Fourier transform infrared (FT-IR) spectroscopy. Human K562 CML cells were exposed to step-wise increasing concentrations of nilotinib, and sub-clones of K562 cells resistant to 50 nM nilotinib were generated and referred to as K562/NIL-50 cells. Antiproliferative effects of nilotinib were determined by XTT cell proliferation assay. Changes in macromolecules in parental and resistant cells were studied by FT-IR spectroscopy. Nilotinib resistance caused significant changes which indicated increases in the level of glycogen and membrane/lipid order. The amount of unsaturated lipids increased in the nilotinib resistant cells indicating lipid peroxidation. The total amount of lipids did not change significantly but the relative proportion of cholesterol and triglycerides altered considerably. Moreover, the transcriptional status decreased but metabolic turn-over increased as revealed by the FT-IR spectra. In addition, changes in the proteome and structural changes in both proteins and the nucleus were observed in the K562/NIL-50 cells. Protein secondary structural analyses revealed that alpha helix structure and random coil structure decreased, however, anti-parallel beta sheet structure, beta sheet structure and turns structure increased. These results indicate that the FT-IR technique provides a method for analyzing drug resistance related structural changes in leukemia and other cancer types.
Authors:
C Ceylan; A Camgoz; Y Baran
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-15
Journal Detail:
Title:  Technology in cancer research & treatment     Volume:  -     ISSN:  1533-0338     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140941     Medline TA:  Technol Cancer Res Treat     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Izmir Institute of Technology, Department of Food Engineering, Urla, Izmir, Turkey. cagatayceylan@iyte.edu.tr.
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