The A₃ adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB signal transduction pathways

The A₃ adenosine receptor (A₃AR) is highly expressed in tumors and was suggested as a target for cancer treatment. In this study, we show that A₃AR is highly expressed in tumor tissues and in peripheral blood mononuclear cells (PBMCs) derived from patients with HCC, as well as from HCC tumor-bearing rats. The high expression level of the receptor was directly correlated to overexpression of NF-κB, known as a transcription factor of A₃AR. CF102, a synthetic highly selective agonist to A₃AR induced a marked dose response inhibition of tumor growth in N1S1 HCC tumor rats, via de-regulation of the NF-κB and the Wnt signal transduction pathways, resulting in apoptosis of tumor cells. Taken together, A₃AR is highly expressed in tumors and PBMCs of HCC patients and tumor-bearing rats. CF102 induced apoptosis and tumor growth inhibition. These data suggest A₃AR as a novel targeted therapy to treat HCC.