A₃ Receptors Are Overexpressed in Pleura from Patients with Mesothelioma and Reduce Cell Growth via Akt/Nuclear Factor-κB Pathway

Abstract

These new findings suggest that A₃AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full-blown MM.

The A3Adenosine Receptor: History and Perspectives

“…Inhibition of Akt is triggered by A 3 AR for the reduction of LPS-mediated hypoxiainducible-factor 1a (HIF-1a) accumulation in murine astrocytes . Downregulation of the PI3K/Akt-NF-kB signaling pathway has also been observed in the inhibitory effect of IB-MECA in adjuvantinduced arthritis and in mesothelioma Madi et al, 2007;Varani et al, 2011a). Recently, it was reported that A 3 AR suppresses angiogenesis by inhibiting PI3K/Akt/mammalian target of rapamycin signaling in endothelial cells (Kim et al, 2013).…”

“…Finally, very high A 3 AR protein expression was observed in a variety of cancer cell lines (Gessi et al, , 2007Merighi et al, 2001Merighi et al, , 2009Suh et al, 2001;Morello et al, 2009;Jajoo et al, 2009;Cohen et al, 2011;Hofer et al, 2011;Varani et al, 2011aVarani et al, , 2013Kanno et al, 2012;Nogi et al, 2012;Kamiya et al, 2012;Otsuki et al, 2012;Vincenzi et al, 2012;Nagaya et al, 2013;Sakowicz-Burkiewicz et al, 2013;Madi et al, 2013) and in cancer tissues (Gessi et al, 2004a;Madi et al, 2004;Bar-Yehuda et al, 2008;Varani et al, 2011a), thus suggesting a role for this subtype as a tumoral marker.…”

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

“…Capadenoson (15) (Ohaion et al, 2009;Varani et al, 2010Varani et al, , 2011. The physiology of A 3 signaling is especially complex because of major differences between rodent and primate species in receptor function and tissue distribution.…”

Purines, Purinergic Receptors, and Cancer

“…Finally, adenosine is also active on tumor cells (7). However, it is not yet clear whether administration of P1 agonists or antagonists will be beneficial or detrimental, due to the different P1 subtypes expressed and the different dosedependent effects on proliferation, VEGF release, and apoptosis; current evidence suggests that targeting A3 receptors might be a promising anticancer strategy (63).…”