title: Synthetic inhibitors of galectin-1 and -3 selectively modulate homotypic cell aggregation and tumor cell apoptosis.
abstract: 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.
  
  
  METHODS
  A series of structural analogs of the disaccharide methyl beta-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology and Neurosciences, Foundation University G. D'Annunzio Chieti-Pescara, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Iurisci
authors.forename: Albana
authors.initials: A
authors.lastname: Cumashi
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Sherman
authors.forename: Yury E
authors.initials: YE
authors.lastname: Tsvetkov
authors.forename: Nicola
authors.initials: N
authors.lastname: Tinari
authors.forename: Enza
authors.initials: E
authors.lastname: Piccolo
authors.forename: Maurizia
authors.initials: M
authors.lastname: D'Egidio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Adamo
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev