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The increment in the uptake of glycerol across the cell membrane by Aquaporin-3 has been associated with large ATP content and intracellular phosphorylation status, conditions associated with a larger proliferation capacity (1,2). Recently, the gold (III) complex Auphen has been described as a very selective and potent inhibitor of AQP3 glycerol permeability (3). Then, we decided to further explore the effect that this selective inhibitor produces on the cell proliferation of cell lines that considerable express AQP3 in a natural way (A431) or cells which are stably or transiently transfected for expression of this protein (PC12 or HEK293T), and compare it with cells with low/or none AQP3 expression (NIH-3T3 and PC12-wt). Proliferation rate was evaluated by two methods: first, by counting the number of viable cells that exclude the trypan blue colorant, after 24 and 48h of culture in the presence or not of 5µM Auphen, using a Neubauer haemocytometer; and second, calculating by immunofluorescence staining, the percentage of cells that incorporate BrdU after 2, 4, 6, 8 and 24h of treatment, in the presence or not of Auphen. Lack of cytotoxic effect of Auphen was previously confirmed by cell counting and using a colorimetric assay that evaluates cellular mitochondrial dehydrogenases activity as readout of number of viable cells. Treatment with Auphen strongly reduced the proliferation process of cells that express AQP3. Conversely, Auphen did not reduce the proliferation of cells with low/ or none expression of AQP3. Flow cytometric analysis of the cell cycle phases performed in PC12 over expressing AQP3 showed that the percentage of cells in the G2/M phase, the most proliferative phase, was higher, and lower the percentage of cells in G0/G1 phase, compare to PC12-wt. Additionally, lower percentage of cells in subG0/G1 phase during cell cycle analysis, as well as lower Annexin V specific staining performed in the presence of Nocodazole (5µM), a potent apoptotic inducer, indicates higher resistance to apoptosis in the over expressing AQP3 cells. Finally we analyzed the possible effect that Auphen may have over the cell cycle pattern that could explain the cell proliferation arrest indicated previously. Overall our results demonstrate a significant role of AQP3 in the cell proliferation process and may indicate a potential therapeutic effect of Auphen over tumorogenis. In tissues with large expression of AQP3 as the skin, epidermoid carcinomas and other skin cancer types could benefit from Auphen treatment due to its capacity of interfere in the cell proliferation associated with AQP3, but more studies are necessary to dig inside the molecular basis that underline to this mechanism(s). [ABSTRACT FROM AUTHOR]