Synthetic inhibitors of galectin-1 and -3 selectively modulate homotypic cell aggregation and tumor cell apoptosis.
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.
Iurisci
Ida
I
Department of Oncology and Neurosciences, Foundation University G. D'Annunzio Chieti-Pescara, Italy.
Cumashi
Albana
A
Sherman
Andrei A
AA
Tsvetkov
Yury E
YE
Tinari
Nicola
N
Piccolo
Enza
E
D'Egidio
Maurizia
M
Adamo
Vincenzo
V
Natoli
Clara
C
Rabinovich
Gabriel A
GA
Iacobelli
Stefano
S
Nifantiev
Nikolay E
NE