Determination of the autophagy signalling pathway triggered by lectin aiming at identifying new targets for drugs to treat leukemia

• Grant number: 13/24201-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2014
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Maria Cristina Roque Antunes Barreira
• Grantee: Sandro Gomes Soares
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 15/08560-0 - Evaluating intracellular targets of ArtinM to trigger cell death events on leukemia cells, BE.EP.PD

Abstract

The development of drugs to treat cancers remains a big challenge for researchers. Even for those diseases using well-standardized protocols and effective drugs, there is always the risk of the patient to become refractory to the treatment due to resistance. In order to develop new drugs, several strategies of cell death are being studied and one of them is the induction of autophagy.Autophagy occurs at basal levels in most cells, acting on cytoplasmic remodeling and eliminating organelles when necessary. Autophagy is a key regulator of many physiological and disease processes and mediates the removal of protein oligomers and various pathogens. Autophagy may be deregulated in several conditions, including metabolic diseases, neurodegenerative disorders, infectious diseases and cancer. The role of autophagy in cancer treatment, especially those of hematologic origin, remains double faced. However, some pro-autophagic drugs have been presented as potential for the use in the treatment of this disease.We have recently described the selective action of a lectin on leukemic cells of myeloid origin. All the results indicate that the ArtinM lectin is capable of inducing cell death independent of caspase activation, and with features of autophagy.Our aim in this project is to characterize the events that lead these cells to death by confirming the induction of autophagy and describing the lectin-induction signaling pathway. With the description of this pathway, we postulate to work in the future with the design of drugs with clinical potential capable of mimetizing the lectin action.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TREVISANI, MARCEL M.; HANNA, EBERT S.; OLIVEIRA, ALINE F.; CARDOSO, SILVIA A.; ROQUE-BARREIRA, MARIA C.; SOARES, SANDRO G.. Vaccination of Mice with Virulence-Associated Protein G (VapG) Antigen Confers Partial Protection against Rhodococcus equi Infection through Induced Humoral Immunity. FRONTIERS IN MICROBIOLOGY, v. 8, MAY 11 2017. (13/24201-5)