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Attiki: International Institute of Anticancer Research
Erscheinungsjahr
2009
Quelle
MEDLINE
Beschreibungen/Notizen
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.