Journal
ACTA PHARMACOLOGICA SINICA
Volume 27, Issue 9, Pages 1175-1184Publisher
NATURE PUBLISHING GROUP
DOI: 10.1111/j.1745-7254.2006.00364.x
Keywords
apoptosis; cell-cycle arrest; guanosine 5 ' triphosphate; differentiation; KG1; U937
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Aim: The differentiation capability of guanosine S-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 mu mol/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, 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.
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