MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt's Lymphoma Cells to Trigger Apoptosis through Multiple Pathways

Mar Drugs. 2015 Dec 14;13(12):7377-89. doi: 10.3390/md13127071.


MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis); shows strong binding affinity to globotriose (Gb3: Galα1-4Galβ1-4Glc). MytiLec revealed β-trefoil folding as also found in the ricin B-subunit type (R-type) lectin family, although the amino acid sequences were quite different. Classification of R-type lectin family members therefore needs to be based on conformation as well as on primary structure. MytiLec specifically killed Burkitt's lymphoma Ramos cells, which express Gb3. Fluorescein-labeling assay revealed that MytiLec was incorporated inside the cells. MytiLec treatment of Ramos cells resulted in activation of both classical MAPK/ extracellular signal-regulated kinase and extracellular signal-regulated kinase (MEK-ERK) and stress-activated (p38 kinase and JNK) Mitogen-activated protein kinases (MAPK) pathways. In the cells, MytiLec treatment triggered expression of tumor necrosis factor (TNF)-α (a ligand of death receptor-dependent apoptosis) and activation of mitochondria-controlling caspase-9 (initiator caspase) and caspase-3 (activator caspase). Experiments using the specific MEK inhibitor U0126 showed that MytiLec-induced phosphorylation of the MEK-ERK pathway up-regulated expression of the cyclin-dependent kinase inhibitor p21, leading to cell cycle arrest and TNF-α production. Activation of caspase-3 by MytiLec appeared to be regulated by multiple different pathways. Our findings, taken together, indicate that the novel R-type lectin MytiLec initiates programmed cell death of Burkitt's lymphoma cells through multiple pathways (MAPK cascade, death receptor signaling; caspase activation) based on interaction of the lectin with Gb3-containing glycosphingolipid-enriched microdomains on the cell surface.

Keywords: Burkitt’s lymphoma cells; JNK; MEK/ERK; MytiLec; Mytilus galloprovincialis; R-type lectin; TNF-α; caspase-9/3; globotriose (Gb3); p21: p38 kinase; β-trefoil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / pathology
  • Butadienes / pharmacology
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Humans
  • K562 Cells
  • Lectins / isolation & purification
  • Lectins / pharmacology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Mytilus / metabolism
  • Nitriles / pharmacology
  • Trisaccharides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Butadienes
  • Lectins
  • Nitriles
  • Trisaccharides
  • Tumor Necrosis Factor-alpha
  • U 0126
  • globotriose
  • Mitogen-Activated Protein Kinases
  • Caspase 3
  • Caspase 9