Structural Prediction and Characterization of Canavalia grandiflora (ConGF) Lectin Complexed with MMP1: Unveiling the Antiglioma Potential of Legume Lectins

Molecules. 2022 Oct 20;27(20):7089. doi: 10.3390/molecules27207089.

Abstract

A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for recognition and therapy. More specifically, lectins can interact with glycan structures found on the malignant cell surface. In this context, the present work aimed to investigate the antiglioma potential of ConGF, a lectin purified from Canavalia grandiflora seeds, against C6 cells. The treatment of C6 cells with ConGF impaired the mitochondrial transmembrane potential, reduced cell viability, and induced morphological changes. ConGF also induced massive autophagy, as evaluated by acridine orange (AO) staining and LC3AB-II expression, but without prominent propidium iodide (PI) labeling. The mechanism of action appears to involve the carbohydrate-binding capacity of ConGF, and in silico studies suggested that the lectin can interact with the glycan structures of matrix metalloproteinase 1 (MMP1), a prominent protein found in malignant cells, likely explaining the observed effects.

Keywords: Canavalia grandiflora; glioblastoma; lectin; matrix metalloproteinase 1.

MeSH terms

  • Acridine Orange
  • Canavalia* / chemistry
  • Carbohydrates / analysis
  • Fabaceae* / chemistry
  • Lectins / chemistry
  • Matrix Metalloproteinase 1
  • Plant Lectins / chemistry
  • Propidium
  • Seeds / chemistry

Substances

  • Lectins
  • Matrix Metalloproteinase 1
  • Propidium
  • Acridine Orange
  • Plant Lectins
  • Carbohydrates

Grants and funding

This study was supported by: the National Council for Scientific and Technological Development (CNPq) Brazil (Projects #439601/2018-5 and #309048/2019-2); CNPq/RENORBIO (Project #407945/2013–0); National Coordination for the Training and Improvement of Higher Education Personnel (CAPES) Brazil via Finance Code 001. This study was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação Cearense de Apoio ao Desenvolvimento Científico e tecnológico (FUNCAP). R.B.L., K.S.N. and B.S.C. are senior investigators of CNPq.