ABSTRACT
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 A[1] receptor and sometimes this effect was receptor independent. The researches showed a differential cytotoxic effect of adenosine and its A[3] agonists on cancerous cells, while other studies demonstrated tumor promoting effect of adenosine and its A[1] agonists. The purpose of the present study was the evaluation of the possible selective anti-tumor effect of A1 receptor agonists on cancerous cells. The substances of N6-cyclohexyl-adenosine [CHA, A[1] agonist], R-isomer of N6-phenylisopropyladenosine [R-PIA, A[1] agonist] and N5-ethylcarboxamido-adenosine [NECA, adenosine A[1]-A[2] non-specific agonist] were tested for their anti-proliferative 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. CHA inhibited cell proliferation in three cell lines [in concentration of 5-50 micro M] and R-isomer of R-PIA in one cell line [in concentration of 10-50 micro M]. 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]. 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 A[1] adenosine receptor agonists have a good potential of specific anti-tumor activity