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Int. J. Mol. Sci. 2019, 20(1), 230; https://doi.org/10.3390/ijms20010230

Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways

1
Université de Toulouse, Cancer Research Center of Toulouse, INSERM UMR 1037, 2 Avenue Hubert Curien, 31037 Toulouse, France
2
Université de Toulouse, UMR 152 PharmaDev, Université Paul Sabatier, Institut de Recherche et Développement, Faculté de Pharmacie, 35 Chemin des Maraîchers, 31062 Toulouse, France
3
Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium
*
Author to whom correspondence should be addressed.
Received: 11 December 2018 / Revised: 30 December 2018 / Accepted: 31 December 2018 / Published: 8 January 2019
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Abstract

Morniga-G, the Gal-specific black mulberry (Morus nigra) lectin, displays high affinity for T (CD176) and Tn (CD175) antigens, frequently expressed at the cancer cell surface. The effects of Morniga-G were investigated on a Tn-positive leukemic Jurkat cell line. The lectin, used in a concentration range between 5–20 μg/mL, induced cell death in leukemic Jurkat cells. Microscopic and cytofluorometric analyses indicated that Jurkat cell death was essentially apoptotic, associated with an increase in the ceramide content and a depolarization of the mitochondrial transmembrane potential. This lectin-mediated cell death was inhibited by the pan caspase-inhibitor zVAD. In addition, cleavage of caspases 8, 9, and 3 was observed in Morniga-G-treated Jurkat cells whereas Jurkat cell lines that are deficient in caspase 8–10, caspase 9, or FADD, survived to the lectin-mediated toxicity. Furthermore, in the presence of TRAIL- or DR5-blocking mononoclonal antibodies, Jurkat cells became resistant to Morniga-G, suggesting that the lectin triggers cell death via the TRAIL/DR5 pathway. In silico computer simulations suggest that Morniga-G might facilitate both the DR5 dimerization and the building of TRAIL/DR5 complexes. Finally, upon treatment of Jurkat cells with benzyl-GalNAc, an O-glycosylation inhibitor, a decrease in Tn antigen expression associating with a reduced Morniga-G toxicity, was observed. Taken together, these results suggest that Morniga-G induces the cell death of Tn-positive leukemic cells via concomitant O-glycosylation-, caspase-, and TRAIL/DR5-dependent pathways. View Full-Text
Keywords: plant lectin; Morniga-G; O-glycosylation; T/Tn antigen; Jurkat cells; cancer cell death; apoptosis; TRAIL/DR5 pathway plant lectin; Morniga-G; O-glycosylation; T/Tn antigen; Jurkat cells; cancer cell death; apoptosis; TRAIL/DR5 pathway
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Poiroux, G.; Barre, A.; Simplicien, M.; Pelofy, S.; Segui, B.; Van Damme, E.J.M.; Rougé, P.; Benoist, H. Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways. Int. J. Mol. Sci. 2019, 20, 230.

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