Comparative Studies of the Effects of Adenosine and ATP on All-trans Retinoic Acid, 1,25-dihydroxy-vitamin D3 and Phorbol 12-myristate 13-acetate-induced Differentiation in U937 Human Leukemia Cells

Adenosine and ATP have been implicated in the regulation of inflammatory responses. Furthermore, adenosine and ATP affect cell growth, cell differentiation, and apoptosis. The aim of this study was to evaluate the differentiation-inducing effects of adenosine and ATP on human monocytic leukemia U937 cells. Adenosine at 10 -3 M markedly induced differentiation in leukemia U937 cells as assessed by evaluating the expression of CD11b. Similarly, ATP at 10 -4 and 10 -3 M significantly induced differentiation in U937 cells. Simultaneously, adenosine at 10 -3 M and ATP at 10 -4 and 10 -3 M significantly inhibited the cell number in U937 cells. Next, we evaluated the effects of adenosine and ATP on U937 cells differentiated by differentiation inducers all-trans retinoic acid (ATRA), 1,25-dihydroxy-vitamin D 3 , (VD 3 ) and phorbol. 12-myristate 13-acetate (PMA). Interestingly, adenosine at 10 -4 and 10 -3 M significantly potentiated ATRAinduced CD11b expression. However, ATRA failed to affect adenosine at 10 -3 M-induced CD11b expression. Similarly, ATP at 10 -4 and 10 -3 M significantly potentiated ATRA-induced CD11b expression. In addition, ATRA potentiated ATP-induced CD11b expression. In contrast, VD 3 and PMA further increased the expression of CD11b in the presence of adenosine or ATP, respectively. These results suggest that adenosine and ATP may induce differentiation in human leukemia U937 cells, and may further increase ATRAinduced differentiation in U937 cells.