Selective Inhibitory Effect of Adenosine A1 Receptor Agonists on the Proliferation of Human Tumor Cell Lines

Background: In this study, the effects of three structural analogues of adenosine upon proliferation of human tumor cells were investigated. Previous research showed a cytotoxic effect of adenosine via A3 receptor and A1 receptor and sometimes this effect was receptor independent. The researches showed a differential cytotoxic effect of adenosine and its A3 agonists on cancerous cells, while other studies demonstrated tumor promoting effect of adenosine and its A1 agonists. The purpose of the present study was the evaluation of the possible selective anti-tumor effect of A1 receptor agonists on cancerous cells. Methods: The substances of N6-cyclohexyl-adenosine (CHA, A1 agonist), R-isomer of N6-phenylisopropyladenosine (R-PIA, A1 agonist) and N5-ethylcarboxamido-adenosine (NECA, adenosine A1-A2 non-specific agonist) were tested for their antiproliferative effect using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. Hep G2, Hep2, CACO2, ACHN and L929 cell lines were used in this assay. Results: CHA inhibited cell proliferation in three cell lines (in concentration of 5-50 µM) and R-isomer of R-PIA in one cell line (in concentration of 10-50 µM). These effects were inhibited partially by addition of 1,3-Dipropyl-8-cyclopentylxanthine (A1 antagonist). The NECA analogue had no inhibitory effect on the cell proliferations. All of the substances had no cytotoxic effect on L929 cells (mouse connective tissue fibroblast cell line). Conclusion: CHA and R-PIA had inhibitory effect on the proliferation of human tumor cell lines partially via A1 receptor, while they didn't show such effect on fibroblast cells. These results suggest that A1 adenosine receptor agonists have a good potential of specific anti-tumor activity.