title: The lectin BJcuL induces apoptosis through TRAIL expression, caspase cascade activation and mitochondrial membrane permeability in a human colon adenocarcinoma cell line.
abstract: It has been demonstrated that the cytotoxic effect of BJcuL, the lectin isolated from Bothrops jararacussu venom, on human gastric carcinoma is accompanied by the inhibition of extracellular matrix adhesion, cytoskeleton disassembly and apoptosis induction. The present study aimed to evaluate the apoptosis mechanisms triggered by the BJcuL interaction with specific glycans on the surface of HT29 human colon adenocarcinoma cells. The results demonstrated that BJcuL interacts with glycoligands targets on the cell, which were inhibited in the presence of d-galactose. It shows a dose-dependently cytotoxic effect that is inhibited in the presence of d-galactose. A dose-dependent cell aggregation decrease was also observed for the HT29 cells. Analysis of cell proliferation inhibition was assessed by anti-PCNA and demonstrated that lectin diminishes PCNA expression when compared with untreated cells. Differences in apoptotic marker expression estimated by immunohistochemistry revealed that the lectin promotes an increase in TRAIL expression, leading to an increase in the expression of FADD, caspase-8 and Bax. Besides the increased expression of apoptosis-related proteins, our results revealed that the lectin promotes a mitochondrial respiration decrease and a 75% increase in the amount of cytochrome c released. Together these results suggest that the cytotoxicity of BJcuL can sensitize pro-apoptotic proteins in the cytoplasm and mitochondria, leading to the apoptotic cascade.
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Danusa de Castro
authors.initials: Dde C
authors.lastname: Damasio
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nolte
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Leonardo Puchetti
authors.initials: LP
authors.lastname: Polak
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Anna Paula
authors.initials: AP
authors.lastname: Brandt
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Natália Borges
authors.initials: NB
authors.lastname: Bonan
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Zischler
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Stuelp-Campelo
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Silvia Maria S C
authors.initials: SM
authors.lastname: Cadena
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Lúcia de
authors.initials: Ld
authors.lastname: Noronha
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil.
authors.forename: Selene L
authors.initials: SL
authors.lastname: Elífio-Esposito
authors.affiliation: Pós-graduação em Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Paraná, 80215-901, Curitiba, Paraná, Brazil. Electronic address: andrea.moreno@pucpr.br.
authors.forename: Andréa Novais
authors.initials: AN
authors.lastname: Moreno-Amaral
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D003435:Crotalid Venoms / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D037181:Lectins, C-Type; D008928:Mitochondria / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: C498078:BJcuL lectin, Bothrops jararacussu; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D020169:Caspases
keywords: Apoptosis; Caspase cascade; Colon adenocarcinoma; Lectin BJcuL; Mitochondria activity; TRAIL expression