ALPHA-SIALYL CHOLESTEROL INCREASES LAMININ IN SCHWANN-CELL CULTURES AND ATTENUATES CYTOSTATIC DRUG-INDUCED REDUCTION OF LAMININ

Schwann cells play an important role in peripheral nerve regeneration. Here, we report the effect of alpha-sialyl cholesterol (alpha-SC), a derivative of the sialic acid-containing natural gangliosides, and the cytostatic agents, cisplatin, taxol and vincristine on the laminin pr oduction in Schwann cell cultures isolated from rat sciatic nerves. La minin, one of several extracellular matrix components produced by Schw ann cells, is known to potentiate axonal outgrowth. Laminin content wa s increased by alpha-SC, starting at 7.0 mu g/ml with a maximal effect at 22.4(.) mu g/ml (30%, P < 0.001). The three cytostatic drugs, dose -dependently reduced laminin content in Schwann cell cultures: (1) cis platin at a threshold dose of 2 mu g/ml (-26.4%, P < 0.001); (2) taxol , starting at a dose of 1 ng/ml (-8.0%, P < 0.05); and (3) vincristine , starting at 0.5 ng/ml (-5.9%, P < 0.05). Cultured Schwann cells were incubated with cytostatic drugs in combination with increasing amount s of alpha-SC and it was found that, depending on the cytostatic drug concentration used, alpha-SC could reduce or completely prevent the cy tostatic drug-induced reduction of laminin in Schwann cell cultures. C o-treatment with alpha-SC also reduced part of the morphological chang es caused by the cytostatic drugs. alpha-SC did not counteract the ant i-proliferative effect of the cytostatic drugs on K-562 human erythrol eukemia cells, In conclusion, alpha-SC increased laminin content in Sc hwann cell cultures and protected Schwann cell cultures against the de crease of laminin by cytostatic drugs without interfering with the ant i-proliferative potential, suggesting that alpha-SC have clinical use in protecting cancer patients against the neurotoxic effects of cytost atic drugs.