A2B adenosine receptor blockade inhibits growth of prostate cancer cells

The role of the A(2B) adenosine receptor (AR) in prostate cell death and growth was studied. The A(2B) AR gene expression quantified by real-time quantitative RT-PCR and Western blot analysis was the highest among four AR subtypes (A(1), A(2A), A(2B), and A(3)) in all three commonly used prostate cancer cell lines, PC-3, DU145, and LNCaP. We explored the function of the A(2B) AR using PC-3 cells as a model. The A(2B) AR was visualized in PC-3 cells by laser confocal microscopy. The nonselective A(2B) AR agonist NECA and the selective A(2B) AR agonist BAY60-6583, but not the A(2A) AR agonist CGS21680, concentration-dependently induced adenosine 3',5'-cyclic monophosphate (cyclic AMP) accumulation. NECA diminished lactate dehydrogenase (LDH) release, TNF-alpha-induced increase of caspase-3 activity, and cycloheximide (CHX)-induced morphological changes typical of apoptosis in PC-3 cells, which were blocked by a selective A(2B) AR antagonist PSB603. NECA-induced proliferation of PC-3 cells was diminished by siRNA specific for the A(2B) AR. The selective A(2B) AR antagonist PSB603 was shown to inhibit cell growth in all three cell lines. Thus, A(2B) AR blockade inhibits growth of prostate cancer cells, suggesting selective A(2B) AR antagonists as potential novel therapeutics.