Metabolic characterization of MDR cancer cells: Evaluation of the effects of glucose and glutamine metabolisms modulation on survival and sensitivity of leukemic cells to the chemotherapeutic imatinib medylate

• Grant number: 11/22444-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2012
• End date: March 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Ana Carolina Santos de Souza Galvão
• Grantee: Melina Bin
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The acquisition of simultaneous resistance to chemotherapeutic agents displaying a variety of chemical structures and different action mechanisms, a phenomenon known as multidrug resistance (MDR), is still the main obstacle in the treatment of cancer patients. Given the situation, hard work has focused on the identification and evaluation of potential modulators mainly the members of the superfamily of ABC transporters. However, clinical trials involving these agents have been quite disappointing that, in part, is associated with the fact that the MDR phenotype is a multifactorial event in wich increased expression of ABC transporters family, despite being a critical event in the acquisition of resistance, is only one of the factors associated with the emergence of MDR phenotype. Nowadays, the consensus is that metabolic transformation plays an active role in tumorigenesis although several aspects of this 'remodeling' of energy metabolism are still not fully known. Additionally, despite the involvement of metabolic alterations in tumor evolution to stages more resistant and aggressive, little is known about the status of specific energy pathways in cells resistant to anticancer treatments and their association with the acquisition of the MDR phenotype. This project proposes to evaluate the energy metabolism of MDR leukemic cells, the use/dependence on glucose and glutamine, and the potential effects of modulation of glycolytic and glutaminolysis metabolisms in the sensitization of cells to the toxic effects of the chemotherapeutic agent imatinib mesylate (Gleevec®). Thus, the development of this project could contribute to a better understanding of energy metabolism in MDR leukemic cells and evaluate the potential use of modulators of glycolytic and glutaminolysis metabolisms as adjuvant therapy for the treatment of tumors resistant to multiple drugs.(AU)