Catfish rhamnose-binding lectin induces G0/1 cell cycle arrest in Burkitt's lymphoma cells via membrane surface Gb3

Glycoconj J. 2017 Feb;34(1):127-138. doi: 10.1007/s10719-016-9739-2. Epub 2016 Oct 28.

Abstract

Silurus asotus egg lectin (SAL), an α-galactoside-binding protein isolated from the eggs of catfish, is a member of the rhamnose-binding lectin family that binds to Gb3 glycan (Galα1-4Galβ1-4Glc). We have previously demonstrated that SAL reduces the proliferation of Gb3-expressing Burkitt's lymphoma Raji cells and confirm here that it does not reduce their viability, indicating that unlike other lectins, it is not cytotoxic. The aim of this study was to determine the signal transduction mechanism(s) underlying this novel SAL/Gb3 binding-mediated effect profile. SAL/Gb3 interaction arrested the cell cycle through increasing the G0/1 phase population of Raji cells. SAL suppressed the transcription of cell cycle-related factors such as c-MYC, cyclin D3, and cyclin-dependent protein kinase (CDK)-4. Conversely, the CDK inhibitors p21 and p27 were elevated by treatment with SAL. In particular, the production of p27 in response to SAL treatment increased steadily, whereas p21 production was maximal at 12 h and lower at 24 h. Activation of Ras-MEK-ERK pathway led to an increase in expression of p21. Notably, treatment of Raji cells with anti-Gb3 mAb alone did not produce the above effects. Taken together, our findings suggest that Gb3 on the Raji cell surface interacts with SAL to trigger sequential GDP-Ras phosphorylation, Ras-MEK-ERK pathway activation, p21 production, and cell cycle arrest at the G0/1 phase.

Keywords: Cell cycle arrest; Extracellular signal-regulated kinase; Globotriaosylceramide; SUEL/rhamnose-binding lectin; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Burkitt Lymphoma / metabolism
  • Catfishes
  • Cell Line, Tumor
  • Cyclin D3 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Fish Proteins / chemistry
  • Fish Proteins / pharmacology*
  • Fish Proteins / toxicity
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Lectins / chemistry
  • Lectins / pharmacology*
  • Lectins / toxicity
  • MAP Kinase Signaling System
  • Neutral Glycosphingolipids / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rhamnose / metabolism

Substances

  • Antineoplastic Agents
  • Cyclin D3
  • Fish Proteins
  • Lectins
  • Neutral Glycosphingolipids
  • Proto-Oncogene Proteins c-myc
  • Cyclin-Dependent Kinase 4
  • Rhamnose