PMID- 16923338
OWN - NLM
STAT- MEDLINE
DCOM- 20071019
LR  - 20171116
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 27
IP  - 9
DP  - 2006 Sep
TI  - Guanosine 5'-triphosphate induces differentiation-dependent apoptosis in human 
      leukemia U937 and KG1 cells.
PG  - 1175-84
AB  - AIM: The differentiation capability of guanosine 5'-triphosphate (GTP) was 
      studied using U937 and KG1 cells. METHODS: Cell cycle was analyzed by PI staining 
      using flow cytometry. Apoptosis was measured by Annexin-V-FITC/PI double staining 
      using flow cytometry. Differentiation was observed by morphological criteria, 
      Wright-Giemsa staining and expression of cell surface markers CD11b and CD14. 
      RESULTS: Variable GTP concentrations (25-200 micromol/L) at short treatment times 
      (up to 24 h) showed significant anti-proliferative activities among both cell 
      types. However, longer treatment times (up to 72 h) were required to trigger 
      apoptosis. Cell-cycle analyses of the GTP-treated cells indicated an increase in 
      S-phase population by 48 h followed by the appearance of a sub-G(1) peak after 72 
      h of treatment. The effects of GTP on U937 and KG1 cells were accompanied with 
      differentiation toward monocyte/macrophage lineage. This was evidenced by a sharp 
      increase in the extent of CD11b and CD14 expression after 24 h of exposure to 
      GTP. The viability of both cell types did not significantly change during the 
      first 24 h. However, at longer treatment times (72-96 h), dramatic decreases in 
      both the extent of CD14 expression and the cell viabilities were observed. 
      Simultaneous measurement of apoptosis and CD14 expression in GTP-treated U937 
      cells indicated that cells with lower CD14 content underwent more apoptosis. 
      CONCLUSION: These finding may pave the way for further pharmaceutical evaluation 
      of GTP as a suitable differentiating agent for acute myeloblastic leukemia (AML) 
      therapy.
FAU - Yazdanparast, Razieh
AU  - Yazdanparast R
AD  - Institute of Biochemistry and Biophysics, P O Box 13145-1384 University of 
      Tehran, Tehran, Iran. yazdan@ibb.ut.ac.ir
FAU - Moosavi, Mohammad Amin
AU  - Moosavi MA
FAU - Mahdavi, Majid
AU  - Mahdavi M
FAU - Lotfi, Abbas
AU  - Lotfi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CD11b Antigen)
RN  - 0 (ITGAM protein, human)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 86-01-1 (Guanosine Triphosphate)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Apoptosis/*drug effects
MH  - CD11b Antigen/metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Differentiation/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Guanosine Triphosphate/administration & dosage/*pharmacology
MH  - Humans
MH  - Leukemia, Myeloid, Acute/metabolism/*pathology
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Time
MH  - U937 Cells
EDAT- 2006/08/23 09:00
MHDA- 2007/10/20 09:00
CRDT- 2006/08/23 09:00
PHST- 2006/08/23 09:00 [pubmed]
PHST- 2007/10/20 09:00 [medline]
PHST- 2006/08/23 09:00 [entrez]
AID - 10.1111/j.1745-7254.2006.00364.x [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2006 Sep;27(9):1175-84. doi: 
      10.1111/j.1745-7254.2006.00364.x.