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. 2007 Aug:7:298-303.
doi: 10.2174/187152207781369878.

The Anti-Cancer Effect of A3 Adenosine Receptor Agonists: A Novel, Targeted Therapy

P Fishman  1 , K A Jacobson  2 , A Ochaion  1 , S Cohen  1 , S Bar-Yehuda  1
Affiliations

The Anti-Cancer Effect of A3 Adenosine Receptor Agonists: A Novel, Targeted Therapy

P Fishman et al. Immunol Endocr Metab Agents Med Chem. 2007 Aug.

Abstract

The A3 adenosine receptor (A3AR) is highly expressed in various human solid tumor cells whereas low expression is found in the adjacent normal tissues. Activation of the A3AR 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 in vitro and in vivo. 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, A3AR agonists may be suggested as a new family of orally bioavailable compounds to be developed as potent inhibitors of malignant diseases.

Keywords: A3 Adenosine receptor; NF-κB.; PKB/Akt; Wnt; anti-cancer effect; synthetic agonists.

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Figures

Fig. (1).
Fig. (1).
The structure of 3 widely used selective A3AR agonists.
Fig. (2).
Fig. (2).
The mechanism of the A3AR-induced growth-inhibitory effect in tumor cells: Involvement of the NF-κB and Wnt signaling pathway.
See this image and copyright information in PMC

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