[Effect of adenosine 5-triphosphate on cell cycle of human acute myeloid leukemia KG1 cells during S phase]

ABSTRACT

Adenosine 5-triphosphate [ATP] not only is the current energy source of all cells but also plays critical role in triggering signaling pathways leading to apoptosis or differentiation. In recent years many investigations have reported anti-cancer activity of ATP on different cell lines. Also several mechanisms have been proposed for its mechanism of action and it appears that the mechanism depends on the cell type. In the present study the effects of ATP on human leukemia KG1 cell line as an experimental model of AML and mechanistic approach was studied. KG1 cells were cultured and treated with different concentrations of the ATP [50-1000 micro M] for various time intervals [24-72 hours]. The Effect of ATP on cell proliferation was studied by MTT assay. Apoptosis was studied by flowcytometery, fluorescent microscopy and DNA fragmentation assay. Cell cycle was analyzed using flowcytometery. The effects of ATP gamma S [un-degradable agonist of ATP] and degradable products of ATP such as AMP, ADP and adenosine were studied to evaluate its mechanism of action. Data were analyzed by student-t-test [p<0.05]. ATP inhibited growth and induced S-phase cell cycle arrest at 24 h to 72 h in concentration between 100-1000 micro m [p<0.05] along with apoptosis. In addition, results showed that these effects of ATP on KG1 cell line were made through P2X[7]receptors. Because current AML therapy methods based on chemotherapy are not so effective and have side effects, according to the results of present study ATP can be used as an effective compound alone or in combination of other drugs to treat of AML