The Anti-Cancer Effect of A Adenosine Receptor Agonists: A Novel, Targeted Therapy.

The A adenosine receptor (AAR) is highly expressed in various human solid tumor cells whereas low expression is found in the adjacent normal tissues. Activation of the AAR with synthetic highly selective agonists, such as IB-MECA, Cl-IB-MECA or LJ529, induces tumor growth inhibition of melanoma, lymphoma, breast, hepatoma, prostate and colon carcinoma cells both and . Two molecular events take place upon receptor activation and include: a. receptor internalization and subsequent degradation, followed by decreased receptor mRNA and protein expression level. b. modulation of down-stream signal transduction pathways, including those related to Wnt and NF-κB. Subsequently, the levels of cyclin D1 and c-Myc are decreased leading to tumor growth inhibition. IB-MECA synergizes with chemotherapeutic agents to yield an additive anti-tumor effect and protects against myelotoxicity induced by chemotherapy. Taken together, AAR agonists may be suggested as a new family of orally bioavailable compounds to be developed as potent inhibitors of malignant diseases.