Lipides, Nutrition, Cancer
Programa de Pós-Graduação em Ciências da Saúde, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
Investigation of animal toxins as antitumoral agents
Background: Venoms are mixtures of peptides and proteins that can act synergistically in vivo leading to complex effects. Individual toxins, however, often have very specific pharmacological effects and have been invaluable tools for probing physiological processes, and for providing leads for drug discovery and development. Among venom components identified as antitumor agents the most cited are phospholipase A2, metalloproteinases, disintegrins, L-aminoacids oxidases and lectins. Lectins are important tools for the investigation of biological events involving protein-carbohydrate interactions. Our group investigated the cytotoxicity of BJcuL, a lectin isolated from the venom of the snake Bothrops jararacussu, on human gastric carcinoma cells (MKN45 and AGS) and human colon adenocarcinoma cells (HT29). BJcuL induced a cell viability decrease in a dose-dependent manner and was able to promote inhibition of cell adhesion to matrigel, effects strongly abolished when the lectin was pre-incubated with the D-Galactose, its specific carbohydrate ligand. BJcuL promoted actin filaments disorganization, DNA fragmentation in addition to mitochondrial respiration decrease and a 75% increase in the amount of cytochrome c released. The mechanisms involved in the actions described for this lectin remains to be described and motivated the collaboration with Dr. Olivier Micheau (University of Burgundy).
1. Damasio, D. ; Nolte, S. ; Noronha, L. ; Zischler, L. F. C. M. ; Cadena, S. M. S. C. ; Elifio-Esposito, S. L. ; Moreno-Amaral, AN . The lectin BJcuL induces apoptosis through TRAIL expression, caspase cascade activation and mitochondrial membrane permeability in a human colon adenocarcinoma cell line. Toxicon (Oxford), v. 90, p. 299-307, 2014.
2. Nolte, S. ; Damasio, D. ; Barea, A.C. ; Magalhães, A. M. ; Zischler, L. F. C. M. ; Stuelp-Campelo, P.M. ; Elifio-Esposito, S. L. ; Reis, C. A. ; Barreira, M. C. R. ; Moreno, A. N. . BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly. Toxicon (Oxford), v. 59, p. 81-85, 2012.
3. Elifio-Esposito, S. L. ; Lopes, P. H. ; Moreno, A. N. ; Ferreira, M. L. ; Ricart, C. A. ; Souza, M. V. ; Zielinski, F. H. ; Becker, J. A. ; Pereira, L. F. A C-type lectin from the venom of Bothrops jararacussu can adhere to extracellular matrix proteins and induce the rolling of leukocytes. Journal of Venomous Animals and Toxins Including Tropical Diseases (Online), v. 13, p. 782-799, 2007.
Invitation: Olivier Micheau - UMR866
Le séminaire aura lieu à la faculté de médecine -Salle Klepping (3ème) à 11h00
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