The understanding of the mechanisms by which a drug acts is essential to determine its specific activity, such as antitumoral actvity. Exogenous guanosine has been suggested as a potential anticancer substance (Song et al, 2005). Here, we investigated phenotypic alterations on B16F10 melanoma cells triggered by guanosine. Guanosine treatment at different concentrations (0,25; 0,5; 1 and 2mM) induced a significant cell growth inhibition  (40% and 50% at 24 and 48h, respectively) when counted by flow cytometry. This inhibition was not associated with cell death (viability by trypan blue exclusion was > 95%), and was accompanied by cellular morphological changes, such as formation of cellular extension. On wound migration assay, cellular migration was inhibited by guanosine treatment (1mM), ca. four fold at 48h. The investigation of the signaling pathways involved showed that guanosine produced a sustained ERK1/2 phosphorylation (30-60 min. after treatment), which may indicate a redifferentiation process. Guanosine effects on cell cycle and on metaloproteases secretion and activity will possibly open new clues for the understanding of guanosine as a possible therapeutic tool. 

Supported by CNPq (412511/2003-7), Fundação Araucária (4779, 5430 e 5672) and CAPES.