Thioridazine-induced apoptosis: studies on mitochondrial outer membrane permeabilization and interaction with Bcl-2 proteins

• Grant number: 14/22467-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 30, 2015
• End date: January 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Tiago Rodrigues
• Grantee: Vivian Werloger Rodrigues de Moraes
• Supervisor: Donald David Newmeyer
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: La Jolla Institute for Allergy and Immunology (LIAI), United States
• Associated to the scholarship: 13/05099-5 - Study of the mechanisms of thioridazine-induced cell death in tumor cells: focus on signaling pathways and expression of BCL-2 family proteins, BP.DR

Abstract

Literature data have shown that psycotropic drugs derived from phenothiazines present antitumor activity. Data from our group have evidenced relevant biological effects of phenothiazines and its analogues in mitochondria, and these effects may be related to the drug capability of inducing cell death. Among the studied phenothiazine derivatives in all models studied, thioridazine was the most potent, which was selected for this present work. Since thioridazine was able to promote mitochondrial dysfunctions associated to cell death in isolated mitochondria, we aim to study more profoundly the effects of this drug on MOMP in whole cells and also to investigate the modulation in the BCL-2 family proteins related to thioridazine-induced cell death. As proposed in this work, the study of thioridazine effects on mitochondria related to cell death in tumor cells and the evaluation of the role of BCL-2 family in this process will contribute to advance the understanding of cancer biology and cancer chemotherapy. (AU)