Effect of heparin derived fractions on the proliferation and protein synthesis of cells in culture.

We investigated the effect of sulfated oligosaccharides derived from depolymerization of heparin on the proliferation and protein synthesis of smooth muscle cells (SMC), hamster kidney (BHK-21) and lung (V-79) fibroblasts, rat hepatoma cells (FAO) and human promyelocytes (HL-60). BHK-21 and FAO showed the highest sensitivity to heparin; V-79 and HL-60 cells were completely resistant. LMWH (Low Molecular Weight Heparin) (MW 4.5 kD) was as effective as unfractionated heparin in reducing cell proliferation. The oligo-derivative 381/1 (MW 2 kD) was effective only on FAO and BHK-21 cells; oligo-derivative 381/2 (MW 1KD) had a negligible effect. The anti-proliferative effect was associated with an increased secretion of some protein classes. This effect was not present in heparin-resistant cells. In conclusion when the molecular size of heparin derivative is reduced below 2 kD (i.e. the size of a hexasaccharide) the anti-proliferative activity decreases dramatically.