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Morniga-G, a T/Tn-specific lectin, induces leukemic cell death via caspase and DR5 receptor-dependent pathways

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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 g/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.
Keywords
plant lectin, Morniga-G, O-glycosylation, T, Tn antigen, Jurkat cells, cancer cell death, apoptosis, TRAIL, DR5 pathway, JACALIN-RELATED LECTINS, T-CELLS, O-GLYCANS, APOPTOSIS, LIGAND, ACTIVATION, EXPRESSION, GLYCOFORM, PROTEINS, ANTIGENS

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MLA
Poiroux, Guillaume, et al. “Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 20, no. 1, 2019, doi:10.3390/ijms20010230.
APA
Poiroux, G., Barre, A., Simplicien, M., Pelofy, S., Ségui, B., Van Damme, E., … Benoist, H. (2019). Morniga-G, a T/Tn-specific lectin, induces leukemic cell death via caspase and DR5 receptor-dependent pathways. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20(1). https://doi.org/10.3390/ijms20010230
Chicago author-date
Poiroux, Guillaume, Annick Barre, Mathias Simplicien, Sandrine Pelofy, Bruno Ségui, Els Van Damme, Pierre Rougé, and Hervé Benoist. 2019. “Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 20 (1). https://doi.org/10.3390/ijms20010230.
Chicago author-date (all authors)
Poiroux, Guillaume, Annick Barre, Mathias Simplicien, Sandrine Pelofy, Bruno Ségui, Els Van Damme, Pierre Rougé, and Hervé Benoist. 2019. “Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 20 (1). doi:10.3390/ijms20010230.
Vancouver
1.
Poiroux G, Barre A, Simplicien M, Pelofy S, Ségui B, Van Damme E, et al. Morniga-G, a T/Tn-specific lectin, induces leukemic cell death via caspase and DR5 receptor-dependent pathways. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2019;20(1).
IEEE
[1]
G. Poiroux et al., “Morniga-G, a T/Tn-specific lectin, induces leukemic cell death via caspase and DR5 receptor-dependent pathways,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 20, no. 1, 2019.
@article{8665354,
  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 g/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.},
  articleno    = {230},
  author       = {Poiroux, Guillaume and Barre, Annick and Simplicien, Mathias and Pelofy, Sandrine and Ségui, Bruno and Van Damme, Els and Rougé, Pierre and Benoist, Hervé},
  issn         = {1422-0067},
  journal      = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
  keywords     = {plant lectin,Morniga-G,O-glycosylation,T,Tn antigen,Jurkat cells,cancer cell death,apoptosis,TRAIL,DR5 pathway,JACALIN-RELATED LECTINS,T-CELLS,O-GLYCANS,APOPTOSIS,LIGAND,ACTIVATION,EXPRESSION,GLYCOFORM,PROTEINS,ANTIGENS},
  language     = {eng},
  number       = {1},
  pages        = {16},
  title        = {Morniga-G, a T/Tn-specific lectin, induces leukemic cell death via caspase and DR5 receptor-dependent pathways},
  url          = {http://dx.doi.org/10.3390/ijms20010230},
  volume       = {20},
  year         = {2019},
}

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