TY - JOUR T1 - Synthetic Inhibitors of Galectin-1 and -3 Selectively Modulate Homotypic Cell Aggregation and Tumor Cell Apoptosis JF - Anticancer Research JO - Anticancer Res SP - 403 LP - 410 VL - 29 IS - 1 AU - IDA IURISCI AU - ALBANA CUMASHI AU - ANDREI A. SHERMAN AU - YURY E. TSVETKOV AU - NICOLA TINARI AU - ENZA PICCOLO AU - MAURIZIA D'EGIDIO AU - VINCENZO ADAMO AU - CLARA NATOLI AU - GABRIEL A. RABINOVICH AU - STEFANO IACOBELLI AU - NIKOLAY E. NIFANTIEV AU - THE CONSORZIO INTERUNIVERSITARIO NAZIONALE PER LA BIO-ONCOLOGIA (CINBO), ITALY Y1 - 2009/01/01 UR - http://ar.iiarjournals.org/content/29/1/403.abstract N2 - 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 β-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. Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -