Multivalency Effects: Example of Synthetic Ganglioside GM3 Analogues in the Study of Antitumor Agents

Ganglioside GM3 (NeuAcα3Galβ4Glcβ1Cer)
is the
simplest sialic acid-containing glycosphingolipid and can inhibit
tumor growth via multiple pathways. Based on the multivalent effect,
we screened mannose-containing GM3 analogues from previously synthesized
GM3 analogues with improved antitumor activity, and it was mutivalently
assembled as di-, tri-, and tetramers (M2, M3, M4). In vitro assays demonstrated that oligomers exhibited stronger cytotoxicity
than the monomer (M1), particularly against B16F10 and HCT116 cells.
Wound healing and transwell assays revealed that M2 and M4 significantly
suppressed migration and invasion in B16F10 and BxPC-3 cells. Western
blot analysis suggested that these compounds inhibit tumor cell movement
by targeting the EGFR/VEGFR-β-catenin signaling pathway and
EMT. These findings highlight the potential of GM3-based oligomers
as anticancer agents.