Copper uptake in mammary epithelial cells activates cyclins and triggers antioxidant response

• Grant number: 15/12381-4
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Duration: October 01, 2015 - March 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Giselle Cerchiaro
• Grantee: Giselle Cerchiaro
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The toxicologic effects of Cu (Cu) on tumor cells have been studied during the past decades, and it is suggested that Cu ion may trigger anti-proliferative effects in vitro. However, in normal cells the toxicologic effects of high exposures of free Cu is not well understood. In this work, we aimed to study the effects of Cu-stimulation on normal epithelial cell cycle proteins and its pro-oxidant activity. Using an integrative approach, we investigated the connection of the Cu entrance in a normal cell with cyclin activation, to determine the connection by which Cu, supplied as soluble salt Cu(II), stimulates the cell cycle of breast epithelial MCF10A cells in vitro. 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 non-tumor 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. (AU)