Anticancer activity study of A3 adenosine receptor agonists

Life Sciences
Gabriella MarucciMeenakshisundaram Kandhavelu

Abstract

A3 adenosine receptor (A3AR) signalling activation seems to mediate anticancer effect, and it has been targeted for drug development. The identification of potent and selective A3AR agonists could be crucial for cancer drug development. In the present study was determined the in vitro activity of known 1-3 and newly 4-6 synthesized compounds with high A3AR affinity and selectivity (Ki in the low nanomolar range) in binding studies. Effect of known and novel A3AR agonists on human prostate cancer (PC3), hepatocellular carcinoma (Hep G2), and epithelial colorectal carcinoma (Caco-2) cells were analysed by cytotoxicity assay, dose and time dependent inhibitor assay, migration, apoptosis, autophagy and reactive oxygen species (ROS) assays. Results show that the anticancer effect is not due to A3AR activation alone. In fact, the more active and selective agonist versus A3AR, compound 1, results inactive on cancer cells such as compounds 2-4. Moreover, results show that the novel compound 5, at micromolar concentration range (IC50 = 28.0 μM), inhibits the growth of PC3, Hep G2, and Caco-2 cells and their migration in time- and dose- dependent manner. The mechanism involved in cell death is attributable to apoptosis. At the same time ...Continue Reading

Citations

Mar 28, 2020·Cells·Wiwin Is EffendiYoshihiro Nishimura
Jul 9, 2020·Cells·Anaí Del Rocío Campos-ContrerasFrancisco G Vázquez-Cuevas
Jan 15, 2021·World Journal of Surgical Oncology·Zhengyu FangWenxi Yan
Sep 11, 2021·Future Medicinal Chemistry·Hien Thi Thu LeMeenakshisundaram Kandhavelu

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