Involvement of copper in biomolecules damage - use of copper(II) complexes in cell culture models simulating the tumor microenvironment

• Grant number: 24/11943-8
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2025
• End date: May 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• 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

Copper can assume the most different geometric forms of coordination, and consequently, its high reactivity and redox activity can be controlled in this way. Being an endogenous element whose cells have full regulatory and transport capacity and redox activity that can be controlled, copper can be used as a potential drug against cancer cells and to cause damage to biomolecules through oxidative stress. Furthermore, recent research shows that excess intracellular copper can lead cells to regulated death through several distinct intracellular mechanisms, one of which is cuproptosis, discovered in 2022. Copper complexes can also bind to DNA, compromising cell division, altering mitochondrial metabolism, generating reactive oxygen species (ROS), and oxidizing lipids and proteins. In this context, the current project seeks to understand in depth the mechanisms of action of copper (II) imine complexes that have been shown to be bioactive in cell culture. The study models will be in glioblastoma and neuroblastoma cell lines formed in 2D culture and also 3D culture in a microtumor environment with THP-1 co-culture (simulating defense cells), through the investigation of the capacity of these complexes (in free and liposomal form of delivery) in altering the cell cycle, compromising genomic stability, altering copper homeostasis and causing the expression of proteins linked to apoptosis and DNA repair. Our objective is to find new forms of action of copper in programmed cell death in tumors and, with this, provide the scientific community with rationales for the development of efficient and promising drugs. (AU)