Article

RNAi depletion of deoxycytidine and deoxyguanosine kinase in human leukemic CEM cells.

Division of Clinical Pharmacology, Department of Medicine and Health, Linköping University, Linköping, Sweden.
Nucleosides Nucleotides &amp Nucleic Acids (impact factor: 0.9). 07/2008; 27(6):712-9. DOI:10.1080/15257770802145231
Source: PubMed

ABSTRACT Resistance toward nucleoside analogues is often due to decreased activities of the activating enzymes deoxycytidine kinase (dCK) and/or deoxyguanosine kinase (dGK). With small interfering RNA (siRNA), dCK and dGK were downregulated by approximately 70% in CEM cells and tested against six nucleoside analogues using the methyl thiazol tetrazolium assay. SiRNA-transfected cells reduced in dCK activity were 3- to 6-fold less sensitive to CdA, AraC, and CAFdA. The sensitivity to AraG and FaraA was unchanged, while the sensitivity toward gemcitabine was significantly increased. dGK depletion in cells resulted in lower sensitivity to FaraA, dFdC, CAFdA, and AraG, but slightly higher sensitivity to CdA and AraC.

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Keywords

6-fold
 
activating enzymes deoxycytidine kinase
 
AraG
 
CdA
 
dCK
 
dCK activity
 
dGK
 
dGK depletion
 
FaraA
 
higher sensitivity
 
methyl thiazol tetrazolium assay
 
nucleoside analogues
 
siRNA
 
SiRNA-transfected cells
 
small