Effects of heparan sulfates with different structures on leukaemia cells: U937 and THP-1 cell differentiation

Heparan sulfates are a proteoglycans consists of a protein core and glycosaminoglycan side chains. These compounds were tested to evaluate their effects on cell differentiation process of U937 and THP-1 cells. The different heparan sulfates including sucrose octasulphate (SOS), di-glucopyranosylamine (DOS), heparin disaccharide I-S sodium salt (HDS-I) and heparin disaccharide III-H sodium salt (HDS-III) were evaluated for inhibition of monocyte-macrophage differentiation process. U937 and THP-1 human monocytes were pre-treated with SOS (10⁻¹¹ to 10⁻⁴ M) for 2h prior to the induction of differentiation with 8nM phorbol 12-myristate 13-acetate(PMA) for 48h. Cell differentiation was determined by morphological examination, cell count, cell proliferation assay and flow cytometry on cell surface markers expression (CD14, CD11a, CD11b and CD68).All the tested heparan sulfates inhibited PMA-induced monocyte-macrophage differentiation, however, the two heparan sulfates (HDS-I and HDS-III) had different disaccharides patterns and charge density compared to SOS and DOS. Heparan sulfates with low di-sulphated disaccharides were less inhibitory at low concentrations. SOS and DOS with high di-sulphated disaccharides produced a significant inhibition of cell differentiation at low concentrations. These contrasting effects of heparan sulfates with different disaccharides patterns and structure on leukaemia cell lines helped to explain the structural-functional relationship-induced inhibitory mechanism pathway on cell differentiation.