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A2B adenosine receptor blockade inhibits growth of prostate cancer cells

Wei Q, Costanzi S, Balasubramanian R, Gao ZG, Jacobson KA.

Purinergic Signal. 2013 Jun;9(2):271-80.

Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA.

Abstract

The role of the A2B adenosine receptor (AR) in prostate cell death and growth was studied. The A2B AR gene expression quantified by real-time quantitative RT-PCR and Western blot analysis was the highest among four AR subtypes (A1, A2A, A2B, and A3) in all three commonly usedprostate cancer cell lines, PC-3, DU145, and LNCaP. We explored the function of the A2B adenosine receptor using PC-3 cells as a model. The A2B adenosine receptor was visualized in PC-3 cells by laser confocal microscopy. The nonselective A2B AR agonist NECA and the selective A2B AR agonist BAY60-6583, but not the A2A 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 A2B adenosine receptor antagonist PSB603. NECA-induced proliferation of PC-3 cellswas diminished by siRNA specific for the A2B adenosine receptor. The selective A2B adenosine receptor antagonist PSB603 was shown to inhibit cell growth in all three cell lines. Thus, A2B adenosine receptor blockade  inhibits growth  of prostate cancer cells, suggesting selective A2B  adenosine receptor antagonists as potential novel therapeutics.

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A2B adenosine receptor blockade inhibits growth of prostate cancer cells-Global Medical Discovery