PMID- 17002868
OWN - NLM
STAT- MEDLINE
DCOM- 20061128
LR  - 20191110
IS  - 1225-8687 (Print)
IS  - 1225-8687 (Linking)
VI  - 39
IP  - 5
DP  - 2006 Sep 30
TI  - GTP induces S-phase cell-cycle arrest and inhibits DNA synthesis in K562 cells 
      but not in normal human peripheral lymphocytes.
PG  - 492-501
AB  - Since differentiation therapy is one of the promising strategies for treatment of 
      leukemia, universal efforts have been focused on finding new differentiating 
      agents. In that respect, we used guanosine 5'-triphosphate (GTP) to study its 
      effects on K562 cell line. GTP, at concentrations between 25-200 microM, 
      inhibited proliferation (3-90%) and induced 5-78% increase in benzidine-positive 
      cells after 6-days of treatments of K562 cells. Flow cytometric analyses of 
      glycophorine A (GPA) showed that GTP can induce expression of this marker in more 
      mature erythroid cells in a time- and dose-dependent manner. These effects of GTP 
      were also accompanied with inhibition of DNA synthesis (measured by 
      [3H]-thymidine incorporation) and early S-phase cell cycle arrest by 96 h of 
      exposure. In contrast, no detectable effects were observed when GTP administered 
      to unstimulated human peripheral blood lymphocytes (PBL). However, GTP induced an 
      increase in proliferation, DNA synthesis and viability of mitogen-stimulated PBL 
      cells. In addition, growth inhibition and differentiating effects of GTP were 
      also induced by its corresponding nucleotides GDP, GMP and guanosine (Guo). In 
      heat-inactivated medium, where rapid degradation of GTP via extracellular 
      nucleotidases is slow, the anti-proliferative and differentiating effects of all 
      type of guanine nucleotides (except Guo) were significantly decreased. Moreover, 
      adenosine, as an inhibitor of Guo transporter system, markedly reduced the GTP 
      effects in K562 cells, suggesting that the extracellular degradation of GTP or 
      its final conversion to Guo may account for the mechanism of GTP effects. This 
      view is further supported by the fact that GTP and Guo are both capable of 
      impeding the effects of mycophenolic acid. In conclusion, our data will hopefully 
      have important impact on pharmaceutical evaluation of guanine nucleotides for 
      leukemia treatments.
FAU - Moosavi, Mohammad Amin
AU  - Moosavi MA
AD  - Institute of Biochemistry and Biophysics, P O Box. 13145-1384, University of 
      Tehran, Tehran, Iran.
FAU - Yazdanparast, Razieh
AU  - Yazdanparast R
FAU - Lotfi, Abbas
AU  - Lotfi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Korea (South)
TA  - J Biochem Mol Biol
JT  - Journal of biochemistry and molecular biology
JID - 9702084
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 12133JR80S (Guanosine)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 85-32-5 (Guanosine Monophosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Cell Differentiation/drug effects
MH  - DNA/*biosynthesis
MH  - Flow Cytometry
MH  - Guanosine/pharmacology
MH  - Guanosine Diphosphate/pharmacology
MH  - Guanosine Monophosphate/pharmacology
MH  - Guanosine Triphosphate/metabolism/*pharmacology
MH  - Humans
MH  - K562 Cells
MH  - Lymphocytes/cytology/*drug effects/metabolism
MH  - Nucleic Acid Synthesis Inhibitors
MH  - S Phase/*drug effects
EDAT- 2006/09/28 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/09/28 09:00
PHST- 2006/09/28 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/09/28 09:00 [entrez]
AID - 10.5483/bmbrep.2006.39.5.492 [doi]
PST - ppublish
SO  - J Biochem Mol Biol. 2006 Sep 30;39(5):492-501. doi: 10.5483/bmbrep.2006.39.5.492.