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-α-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.
Written by:
Wei Q, Costanzi S, Balasubramanian R, Gao ZG, Jacobson KA. Are you the author?
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.
Reference: Purinergic Signal. 2013 Jan 15. (Epub ahead of print)
PubMed Abstract
PMID: 23315335
