Anales RANF

P.69 RESVERATROL ACTS THROUGH ADENOSINE RECEPTORS IN TUMORAL CELL LINES S. Muñoz-López 1 , A. Sánchez-Melgar 1 , JL. Albasanz 1 , M. Martín 1 1 . Universidad de Castilla-La Mancha (UCLM), Ciudad Real, Spain. Extracellular adenosine is one of the major constituents of the tumor microenvironment and plays a crucial role in proliferation, angiogenesis and metastasis in cancer. The effects of this purine are triggered through four G-protein coupled receptors: A 1 , A 2A , A 2B and A 3 . A 1 and A 3 receptors inhibit adenylyl cyclase activity through G i/o protein whereas A 2A and A 2B receptors activate this enzymatic system through G s protein. Current efforts are focused on resveratrol (RSV) action, a diet polyphenolic phytoalexin found in many plant species such as grapes, peanuts and red wine. This molecule has shown promising effects in inhibiting proliferation and cancer progression in several tumoral models. However, its molecular mechanisms are poorly understood. Recently, we have described that RSV acts as a non-selective adenosine receptor agonist. Therefore, the aim of the present work was to study the antitumoral effect of RSV and the possible mechanism involving adenosine receptors. To this end, two tumoral cell lines were used, rat C6 glioma and human HeLa epithelioma cervix cells. Cell viability by XTT method and adenosine receptors quantification by Western- blotting and real time PCR were assayed. Results show that RSV was able to cause cell death in a time and concentration dependent manner in both cell lines. The treatment with this polyphenol caused a modulation of several adenosine receptor types. In addition, 5’-nucleotidase activity and adenosine levels were determined in HeLa cells and it was observed that RSV alters these parameters. As RSV has been shown to be a non-selective adenosine receptors agonist, our results suggest that a possible mechanism underlying antitumoral effect of RSV could be through adenosine receptor binding.