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

摘要: Morniga-G, the Gal-specific black mulberry (Morus nigra) lectin, displays high affinity for T (CD176) and Tn (CD175) antigens, frequently expressed at cancer cell surface. The effects of Morniga-G were investigated on a Tn-positive leukemic Jurkat line. used in concentration range between 5⁻20 μg/mL, induced death cells. Microscopic cytofluorometric analyses indicated that was essentially apoptotic, associated with an increase ceramide content depolarization mitochondrial transmembrane potential. This lectin-mediated inhibited by pan caspase-inhibitor zVAD. In addition, cleavage caspases 8, 9, 3 observed Morniga-G-treated cells whereas lines are deficient caspase 8⁻10, or FADD, survived to toxicity. Furthermore, presence TRAIL- DR5-blocking mononoclonal antibodies, became resistant suggesting lectin triggers via TRAIL/DR5 pathway. silico computer simulations suggest might facilitate both DR5 dimerization building complexes. Finally, upon treatment benzyl-GalNAc, O-glycosylation inhibitor, decrease antigen expression associating reduced toxicity, observed. Taken together, these results induces concomitant O-glycosylation-, caspase-, TRAIL/DR5-dependent pathways.