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oai:repisalud.isciii.es:20.500.12105/225052024-11-29T07:27:34Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Torrens-Mas, Margalida author Hernández-López, Reyniel author Oliver, Jordi author Roca, Pilar author Sastre-Serra, Jorge author 2018-08 Sirtuin 3 (SIRT3) is the major mitochondria deacetylase and regulates ROS levels by targeting several key proteins, such as those involved in mitochondrial function and antioxidant defenses. This way, SIRT3 balances ROS production and scavenging and promotes cell survival. The aim of this study was to analyze the effect of SIRT3 silencing on the antioxidant response in SW620 colon cancer cell line, and whether this intervention could improve efficacy of oxaliplatin, a common drug used to treat colon cancer. For this purpose, we obtained stable clones of SW620 with SIRT3 knockdown and determined parameters such as ROS levels and ROS production, levels of several antioxidant enzymes, cell viability, and apoptosis. Results showed that after SIRT3 silencing, both ROS levels and production were increased, and antioxidant enzymes gene expression was significantly reduced. Furthermore, manganese superoxide dismutase levels and enzymatic activity were reduced. Combination of SIRT3 knockdown with oxaliplatin treatment further increased ROS production and apoptosis, reducing cell viability. Finally, survival curves on colon cancer patients suggested that SIRT3 expression is related to a poorer prognosis. In conclusion, SIRT3 could be a target for colon cancer, since it regulates the antioxidant response and its knockdown improves the efficacy of oxaliplatin treatment. Torrens-Mas M, Hernández-López R, Oliver J, Roca P, Sastre-Serra J. Sirtuin 3 silencing improves oxaliplatin efficacy through acetylation of MnSOD in colon cancer. J Cell Physiol. 2018 Aug;233(8):6067-76. https://hdl.handle.net/20.500.13003/20195 https://hdl.handle.net/20.500.12105/22505 29323702 10.1002/jcp.26443 1097-4652 Journal of cellular physiology 2-s2.0-85043314097 430797600050 L621147390 Sirtuin 3 silencing improves oxaliplatin efficacy through acetylation of MnSOD in colon cancer