The Anti-Tumor Effect of A3 Adenosine Receptors Is Potentiated by Pulsed Electromagnetic Fields in Cultured Neural Cancer Cells

Department of Clinical and Experimental Medicine, Pharmacology Unit, University of Ferrara, Ferrara, Italy.
PLoS ONE (Impact Factor: 3.23). 06/2012; 7(6):e39317. DOI: 10.1371/journal.pone.0039317
Source: PubMed


A(3) adenosine receptors (ARs) play a pivotal role in the development of cancer and their activation is involved in the inhibition of tumor growth. The effects of pulsed electromagnetic fields (PEMFs) on cancer have been controversially discussed and the detailed mechanisms are not yet fully understood. In the past we have demonstrated that PEMFs increased A(2A) and A(3)AR density and functionality in human neutrophils, human and bovine synoviocytes, and bovine chondrocytes. In the same cells, PEMF exposure increased the anti-inflammatory effect mediated by A(2A) and/or A(3)ARs. The primary aim of the present study was to evaluate if PEMF exposure potentiated the anti-tumor effect of A(3)ARs in PC12 rat adrenal pheochromocytoma and U87MG human glioblastoma cell lines in comparison with rat cortical neurons. Saturation binding assays and mRNA analysis revealed that PEMF exposure up-regulated A(2A) and A(3)ARs that are well coupled to adenylate cyclase activity and cAMP production. The activation of A(2A) and A(3)ARs resulted in the decrease of nuclear factor-kappa B (NF-kB) levels in tumor cells, whilst only A(3)ARs are involved in the increase of p53 expression. A(3)AR stimulation mediated an inhibition of tumor cell proliferation evaluated by thymidine incorporation. An increase of cytotoxicity by lactate dehydrogenase (LDH) release and apoptosis by caspase-3 activation in PC12 and U87MG cells, but not in cortical neurons, was observed following A(3)AR activation. The effect of the A(3)AR agonist in tumor cells was enhanced in the presence of PEMFs and blocked by using a well-known selective antagonist. Together these results demonstrated that PEMF exposure significantly increases the anti-tumor effect modulated by A(3)ARs.

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    • "It is still unclear whether EMF are linked or not to health problems such as cancer, but this hypothesis seems unlikely in most cases [49]. Even if mobile phone us‐ age is probably not linked with brain cancer, the capability of EMF to influence cells and ex‐ tracellular matrix are clearly demonstrated [50] [51] [52] [53] [54] [55]. It is therefore crucial to investigate this relation to first prevent potential deleterious exposure that might lead to health problem and second, to understand mechanisms and eventually develop novel medical therapies [56] [57] [58] as well as tissue engineering applications [59] [60] [61] [62] [63]. "

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