Eriksson, Staffan
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences
Abstract
The aim of this study was to clarify the biochemical and molecular mechanisms behind the cross-resistance to nucleoside analogues (NAs) in four erythroleukemic cell lines with acquired resistance to the anthracycline daunorubicin and to the vinca alkaloid vincristine, expressing high levels of p-glycoprotein (P-gp, MDR1). All resistant strains exhibited cross-resistance to NA (cladribine and cytosine arabinoside) -induced apoptosis, assessed by caspase-3-like activation and were less sensitive to NA cytotoxicity in MTT assay. Real-time PCR and enzyme activity analysis showed reduced amounts of deoxycytidine kinase (35-80%) and elevated levels of 5'-nucleotidases (50-100%). The ratio 5'-nucleotidase to deoxycytidine kinase increased between 2.5- and 7.5-folds in resistant cells. This is in agreement with the observation that 5'-nucleotidase/deoxycytidine kinase ratio might be an important factor in predicting resistance to NAs. Implications of this finding for combining anthracyclines or vinca alkaloids with NAs toward leukemic cells are discussed. (C) 2004 Elsevier Inc. All rights reserved.
Keywords
cytosine arabinoside; anthracycline; p-glycoprotein; deoxycytidine kinase.; 5 '-nucleotidase; cladribine
Published in
Biochemical and Biophysical Research Communications
2004, volume: 320, number: 3, pages: 825-832
Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
SLU Authors
Publication identifier
- DOI: https://doi.org/10.1016/j.bbrc.2004.06.016
Permanent link to this page (URI)
https://res.slu.se/id/publ/3561