EFFECTS OF CHONDROITIN SULFATES WITH DIFFERENT STRUCTURES ON LEUKEMIA-CELLS - U-937 CELL-PROLIFERATION AND DIFFERENTIATION

Chondroitin sulfates extracted and purified by different manufacturers were tested to evaluate their effects on proliferation and differenti ation processes of U-937 cells. The different chondroitin sulfates wer e evaluated for purity, structure and physicochemical properties. The three chondroitin sulfates utilized did not present other contaminant glycosaminoglycans and proteins and had about the same relative molecu lar mass but different disaccharide patterns and charge density. Chond roitin sulfates with small amounts of disulfated disaccharides and low charge density, at 5 mug/ml concentration, doubled (about + 133%) cel l proliferation in comparison to controls. In contrast, chondroitin su lfates with large amounts of disulfated disaccharides and high sulfate to carboxyl ratio were less effective (about + 15%) in stimulating ce ll proliferation at low concentration. A decrease of U-937 cell prolif eration was observed in proportion to the increased amounts of chondro itin sulfate with low sulfate to carboxyl ratio. On the contrary, chon droitin sulfate with large amounts of disulfated disaccharides produce d increased cell proliferation depending on concentration. Small amoun ts (5-10 mug/ml) of chondroitin sulfates with low charge density reduc ed the differentiative process of U-937 cells. Chondroitin sulfate wit h large amounts of disulfated disaccharides and high charge density se emed to be able to produce a significant decrease of differentiative p rocesses only at very high concentrations (1000 mug/ml). These contras ting effects of chondroitin sulfates with different disaccharide patte rns (and structure) and charge density on a leukemia cell line could h elp to explain the regulation of proliferative and/or differentiative processes of hemopoietic cells. This is underlined by the changes of t ypes, physicochemical properties and structure of glycosaminoglycans i nduced by different extracellular factors and agents.