title: The recognition of N-glycans by the lectin ArtinM mediates cell death of a human myeloid leukemia cell line.
abstract: ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6)Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC(50) = 10 µg/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment.
authors: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil.
authors: Fernanda Caroline
authors: FC
authors: Carvalho
authors: Sandro Gomes
authors: SG
authors: Soares
authors: Mirela Barros
authors: MB
authors: Tamarozzi
authors: Eduardo Magalhães
authors: EM
authors: Rego
authors: Maria-Cristina
authors: MC
authors: Roque-Barreira
mesh_terms: D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000473:pathology*; D037241:Mannose-Binding Lectins / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D011134:Polysaccharides / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037241:Mannose-Binding Lectins; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D020169:Caspases