The lectin BJcuL induces apoptosis through TRAIL expression, caspase cascade activation and mitochondrial membrane permeability in a human colon adenocarcinoma cell line

• Published in: Toxicon (Oxford) Vol. 90; pp. 299 - 307
• Main Authors: Damasio, Danusa de Castro, Nolte, Stefanie, Polak, Leonardo Puchetti, Brandt, Anna Paula, Bonan, Natália Borges, Zischler, Luciana, Stuelp-Campelo, Patrícia M., Cadena, Silvia Maria S.C., Noronha, Lúcia de, Elífio-Esposito, Selene L., Moreno-Amaral, Andréa Novais
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-11-2014
• Subjects: Activation; Apoptosis; Apoptosis - drug effects; Bothrops jararacussu; Cascades; Caspase cascade; Caspases - metabolism; Colon; Colon adenocarcinoma; Colonic Neoplasms - enzymology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Crotalid Venoms - toxicity; HT29 Cells; Human; Humans; Inhibition; Lectin BJcuL; Lectins; Lectins, C-Type; Mitochondria - drug effects; Mitochondria activity; Permeability - drug effects; Proteins; TNF-Related Apoptosis-Inducing Ligand - metabolism; TRAIL expression; Lectin BJcuL; Mitochondria activity; TRAIL expression; Colon adenocarcinoma; Caspase cascade; Apoptosis
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2014.08.062

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.
•BJcuL activates colon adenocarcinoma apoptosis.•TRAIL expression is increased by the lectin BJcuL.•BJcuL is able to induce Caspases cascade in tumor cells.•BJcuL alter the mitochondria activity and permeability.