title: Copper Uptake in Mammary Epithelial Cells Activates Cyclins and Triggers Antioxidant Response.
abstract: The toxicologic effects of copper (Cu) on tumor cells have been studied during the past decades, and it is suggested that Cu ion may trigger antiproliferative effects in vitro. However, in normal cells the toxicologic effects of high exposures of free Cu are not well understood. In this work, Cu uptake, the expression of genes associated with cell cycle regulation, and the levels of ROS production and related oxidative processes were evaluated in Cu-treated mammary epithelial MCF10A nontumoral cells. We have shown that the Cu additive is associated with the activation of cyclin D1 and cyclin B1, as well as cyclin-dependent kinase 2 (CDK2). These nontumor cells respond to Cu-induced changes in the oxidative balance by increase of the levels of reduced intracellular glutathione (GSH), decrease of reactive oxygen species (ROS) generation, and accumulation during progression of the cell cycle, thus preventing the cell abnormal proliferation or death. Taken together, our findings revealed an effect that contributes to prevent a possible damage of normal cells exposed to chemotherapeutic effects of drugs containing the Cu ion.
authors.affiliation: Center for Natural Sciences and Humanities, Federal University of ABC (UFABC), 09210-170 Santo André, SP, Brazil.
authors.forename: Nathália Villa
authors.initials: NV
authors.lastname: dos Santos
authors.affiliation: Center for Natural Sciences and Humanities, Federal University of ABC (UFABC), 09210-170 Santo André, SP, Brazil.
authors.forename: Andreza Cândido
authors.initials: AC
authors.lastname: Matias
authors.affiliation: Center for Mathematics, Computation and Cognition, Federal University of ABC (UFABC), 09210-170 Santo André, SP, Brazil.
authors.forename: Guilherme Shigueto Vilar
authors.initials: GS
authors.lastname: Higa
authors.affiliation: Center for Mathematics, Computation and Cognition, Federal University of ABC (UFABC), 09210-170 Santo André, SP, Brazil.
authors.forename: Alexandre Hiroaki
authors.initials: AH
authors.lastname: Kihara
authors.affiliation: Center for Natural Sciences and Humanities, Federal University of ABC (UFABC), 09210-170 Santo André, SP, Brazil.
authors.forename: Giselle
authors.initials: G
authors.lastname: Cerchiaro
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000378:metabolism* / Q000633:toxicity*; D056744:Cyclin B1 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D056744:Cyclin B1; D017382:Reactive Oxygen Species; D019938:Cyclin D1; D003300:Copper; D051357:Cyclin-Dependent Kinase 2