Inhibition of human tumour cell proliferation by analogues of adenosine

The effects of adenosine and several structural analogues of adenosine upon thymidine incorporation into human tumour cells and rat cervical lymphocytes were investigated. The analogue NECA, which has equal specificity for the A1 and A2 receptor, had the most inhibitory effect on lymphocyte proliferation while the A1 agonists had limited effects, suggesting that these cells possess principally A2 adenosine receptors. In the case of human tumour cells, however, the most inhibitory effect on proliferation was obtained with the A1-specific analogues. The general order of inhibitory effects of adenosine analogues on thymidine incorporation in human tumour cells was: S-ENBA > CPA = R-PIA > S-PIA > NECA. These findings suggest that in the cells presently studied the A1 adenosine receptor predominates. Removal of exogenous adenosine by growth in the presence of adenosine deaminase inhibited thymidine incorporation. The effect of adenosine removal lends further support to the proposal that adenosine has some, as yet unidentified, regulatory role in the control of human tumour cell proliferation.