Synthetic and plant-derived multivalent galactans as modulators of cancer-associated galectins-3 and -9

Abstract

Galectins are {beta}-galactoside-binding proteins with numerous functions. Some of them are involved in proliferation and metastasis of cancer, making them promising therapeutic targets. As different plant glycans have been shown to bind to galectins, plant saccharides might be potential galectin inhibitors. To produce plant galactans rich in galactose and smaller in size, we degraded arabinogalactan-proteins from Echinacea purpurea and Zostera marina as well as arabinogalactan from larch. As galectin (Gal)-3 and -9 both have been described to be involved in cancer development, we quantified the binding capacities of the different galactans to both galectins by biolayer-interferometry. Our results revealed that all plant-derived galactans and Yariv reagents with terminal galactose and lactose residues bind to Gal-3 in micromolar ranges. Surprisingly, only the higher charged galactans from Zostera marina showed affinity to Gal-9. Investigations of two different pancreatic cancer cell lines (Panc1 and Panc89) and different cell variants thereof revealed that Gal-3 was expressed by both cell lines with a significantly higher Gal-3 level in Panc1 cells compared to Panc89 cells. Conversely, Gal-9 was only detected in Panc89 cells. The findings revealed that galactans are promising sources to develop galectin antagonists and plant galactans from different species express specificities for distinct galectins.