Targeting the A3 adenosine receptor for cancer therapy: Inhibition of prostate carcinoma cell growth by A3AR agonist

Pnina Fishman*, Sara Bar-Yehuda, Eti Ardon, Lea Rath-Wolfson, Faina Barrer, Avivit Ochaion, Lea Madi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Agonists to A3 adenosine receptor (A3AR) were shown to inhibit the growth of various tumor cell types. The present study demonstrates that a synthetic A3AR agonist, 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purine-9-yl]-N-methyl- β-D-ribofura-nuronamide (IB-MECA), inhibits the growth of androgen-independent PC-3 prostate human carcinoma cells and illustrates the molecular mechanism involved. Materials and Methods: PC-3 prostate carcinoma cells were used. Cell growth was examined in vitro by the thymidine incorporation assay and in vivo by inoculating the tumor cells subcutaneously into nude mice and monitoring tumor size. The protein expression level in cells and tumor extracts was tested by Western blot analysis. Results: A decrease in the protein expression level of A3AR and the downstream effector PKAc was observed Consequently, the GSK-3β protein level increased, resulting in the destabilization of β-catenin and the subsequent suppression of cyclin D1 and c-myc expression. IB-MECA treatment also induced down-modulation of the expression of NF-κB/p65, known to regulate the transcription of cyclin D1 and c-Myc. This chain of events occurred both in vitro and in vivo and suggests the use of the above-mentioned signaling proteins as markers to predict tumor cell response to A3AR activation. Conclusion: Taken together we demonstrated that A3AR activation deregulates the Wnt and the NF-κB signaling pathways resulting in the inhibition of prostate carcinoma cell growth.

Original languageEnglish
Pages (from-to)2077-2083
Number of pages7
JournalAnticancer Research
Issue number3 A
StatePublished - May 2003
Externally publishedYes


  • A3 adenosine receptor
  • GSK-3β
  • NF-κB
  • PKA
  • Prostate carcinoma


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