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). <i>In vitro</i> 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.