Antibacterial
peptides (ABPs) with
cancer-selective toxicity have received much more attention as alternative chemotherapeutic agents in recent years. However, the basis of their anticancer activity remains unclear. The modification of cell surface glycosylation is a characteristic of
cancer cells. The present study investigated the effect of glycosylation, in particular
sialic acid, on the anticancer activity of ABPs. We showed that aurein 1.2,
buforin IIb and BMAP-28m exhibited selective cytotoxicity toward MX-1 and MCF-7
breast cancer cells. The binding activity, cytotoxicity and apoptotic activity of ABPs were enhanced by the presence of O-, N-
glycoproteins,
gangliosides and
sialic acid on the surface of
breast cancer cells. Among N-, O-
glycoproteins and
ganglioside, O-
glycoproteins almost had the strongest effect on the binding and cytotoxicity of the three
peptides. Further, up-regulation of hST6Gal1 in CHO-K1 cells enhanced the susceptibility of cells to these
peptides. Finally, the growth of MX-1 xenograft
tumors in mice was significantly suppressed by
buforin IIb treatment, which was associated with induction of apoptosis and inhibition of vascularization. These data demonstrate that the three
peptides bind to
breast cancer cells via an interaction with surface O-, N-
glycoproteins and
gangliosides.
Sialic acids act as key
glycan binding sites for cationic ABP binding to
glycoproteins and
gangliosides. Therefore, glycosylation in
breast cancer cells plays an important role in the anticancer activity of ABPs, which may partly explain their
cancer-selective toxicity. Anticancer ABPs with
cancer-selective cytotoxicity will be promising candidates for anticancer
therapy in the future.