Guanosine 5'-triphosphate induces differentiation-dependent apoptosis in human leukemia U937 and KG1 cells.
OBJECTIVE
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.


CONCLUSIONS
These finding may pave the way for further pharmaceutical evaluation of GTP as a suitable differentiating agent for acute myeloblastic leukemia (AML) therapy.
Yazdanparast
Razieh
R
Institute of Biochemistry and Biophysics, P O Box 13145-1384 University of Tehran, Tehran, Iran. yazdan@ibb.ut.ac.ir
Moosavi
Mohammad Amin
MA
Mahdavi
Majid
M
Lotfi
Abbas
A
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D039481:CD11b Antigen / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006160:Guanosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D013995:Time; D020298:U937 Cells
D000970:Antineoplastic Agents; D039481:CD11b Antigen; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D006160:Guanosine Triphosphate