POTENTIATION OF ANTIPROLIFERATIVE EFFECT OF NITROPRUSSIDE BY ASCORBATE IN HUMAN BRAIN-TUMOR CELLS

The interactions of nitric oxide (NO) and ascorbate were explored on t he control of growth of human brain tumor cells. Sodium nitroprusside, a NO-generating agent, inhibited the growth of SK-N-MC human neurobla stoma cells in a dose-dependent manner. The growth inhibitory effect o f nitroprusside was potentiated by sodium ascorbate and inhibited by h emoglobin. Ascorbate-induced potentiation was also observed in U-373 M G human astrocytoma cells. In both tumor cell lines, this potentiation was blocked by catalase, suggesting that hydrogen peroxide may be inv olved in the potentiation mechanism. In astrocytoma cells, mannitol or deferoxamine also reversed ascorbate-induced potentiation, indicating involvement of hydroxyl radical. These results suggest that the combi ned treatment with nitroprusside and ascorbate may be a valuable thera peutic strategy for brain tumors.