IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
SYNTHETIC INHIBITORS OF GALECTINS-1 AND -3 SELECTIVELY MODULATE DIFFERENT STEPS OF TUMOR PROGRESSION
Autor/es:
IDA IURISCI; ALBANA CUMASHI; ANDREI SHERMAN; NICOLA TINARI; ENZA PICCOLO; MAURIZIA DEGIDIO; YURI TSETKOV; GABRIEL RABINOVICH; NIKOLAY NIFANTIEV; STEFANO IACOBELLI
Revista:
ANTICANCER RESEARCH
Editorial:
J. DELINASSIOS
Referencias:
Lugar: ATENAS; Año: 2009 vol. 29 p. 403 - 410
ISSN:
0250-7005
Resumen:
Background: Galectins have emerged as critical regulators of tumor progression and metastasis, by modulating different biological events including homotypic cell aggregation, apoptosis, migration, angiogenesis and immune escape. Therefore, galectin inhibitors might represent novel therapeutic agents for cancer. Materials and Methods: A series of structural analogs of the disaccharide methyl â-lactosaminide were screened as potential galectin inhibitors by examining their capability to block binding of galectin-1 and/or galectin-3 to LGalS3BP in solid-phase assays. To demonstrate any functional role in vitro, oligosaccharides were characterized by their ability to regulate tumor cell apoptosis and LGalS3BP-induced homotypic cell aggregation. Results: Oligosaccharides differentially inhibited binding of each galectin to LGalS3BP. Compounds containing longer oligosaccharide chains were found to be potent inhibitors of both galectins under static conditions. Strikingly, the most active compound in inhibiting homotypic cell aggregation and tumor cell apoptosis was found to be allyl lactoside, which paradoxically exhibited a modest inhibitory capacity for blocking galectin-1 and -3 binding to LGalS3BP. Conclusion: Allyl lactoside represents a novel powerful inhibitor of tumor-associated homotypic cell aggregation and apoptosis. Further investigations are required to remodel selective and potent inhibitors capable of specifically modulating the activity of different members of the galectin family.