Pons, Daniel-GabrielNadal-Serrano, MercedesTorrens-Mas, MargalidaValle, AdamoOliver, JordiRoca, Pilar2024-07-042024-07-042015-09Pons DG, Nadal-Serrano M, Torrens-Mas M, Valle A, Oliver J, Roca P. UCP2 inhibition sensitizes breast cancer cells to therapeutic agents by increasing oxidative stress. Free Radic Biol Med. 2015 Sep;86:67-77.https://hdl.handle.net/20.500.13003/20198http://hdl.handle.net/20.500.12105/20134This is an postprint (Accepted Manuscript) of an article published by Elsevier in Free Radical Biology and Medicine on 2015 May 7, available online: https://doi.org/10.1016/j.freeradbiomed.2015.04.032Modulation of oxidative stress in cancer cells plays an important role in the study of the resistance to anticancer therapies. Uncoupling protein 2 (UCP2) may play a dual role in cancer, acting as a protective mechanism in normal cells, while its overexpression in cancer cells could confer resistance to chemotherapy and a higher survival through downregulation of ROS production. Thus, our aim was to check whether the inhibition of UCP2 expression and function increases oxidative stress and could render breast cancer cells more sensitive to cisplatin (CDDP) or tamoxifen (TAM). For this purpose, we studied clonogenicity, mitochondrial membrane potential (??m), cell viability, ROS production, apoptosis, and autophagy in MCF-7 and T47D (only the last four determinations) breast cancer cells treated with CDDP or TAM, in combination or without a UCP2 knockdown (siRNA or genipin). Furthermore, survival curves were performed in order to check the impact of UCP2 expression in breast cancer patients. UCP2 inhibition and cytotoxic treatments produced a decrease in cell viability and clonogenicity, in addition to an increase in ??m, ROS production, apoptosis, and autophagy. It is important to note that CDDP decreased UCP2 protein levels, so that the greatest effects produced by the UCP2 inhibition in combination with a cytotoxic treatment, with regard to treatment alone, were observed in TAM+UCP2siRNA-treated cells. Moreover, this UCP2 inhibition caused autophagic cell death, since apoptosis parameters barely increased after UCP2 knockdown. Finally, survival curves revealed that higher UCP2 expression corresponded with a poorer prognosis. In conclusion, UCP2 could be a therapeutic target in breast cancer, especially in those patients treated with tamoxifen.enghttp://creativecommons.org/licenses/by-nc-nd/4.0/Breast NeoplasmsCisplatinDisease-Free SurvivalOxidative StressKaplan-Meier EstimateReactive Oxygen SpeciesHumansAntineoplastic AgentsMitochondrial ProteinsAutophagyMCF-7 CellsCell SurvivalIon ChannelsMembrane Potential, MitochondrialApoptosisTamoxifenFemaleUncoupling Protein 2Drug Resistance, NeoplasmGene Knockdown Techniquesresearch articleAttribution-NonCommercial-NoDerivatives 4.0 Internacional25960046866710.1016/j.freeradbiomed.2015.04.0321873-4596Free radical biology & medicineopen accessResistencia a AntineoplásicosCanales IónicosFemeninoCélulas MCF-7ApoptosisProteínas MitocondrialesTamoxifenoSupervivencia CelularAntineoplásicosAutofagiaHumanosEstimación de Kaplan-MeierEspecies Reactivas de OxígenoProteína Desacopladora 2Estrés OxidativoCisplatinoNeoplasias de la MamaSupervivencia sin EnfermedadTécnicas de Silenciamiento del GenPotencial de la Membrana Mitocondrial2-s2.0-84934764668360569700008L605075422