Antitumor effects of vitamin A and inhibitors of ornithine decarboxylase in cultured neuroblastoma and glioma cells

Abstract

The antiproliferative effects of vitamin A analogs and difluoromethyl ornithine, an irreversible inhibitor of ornithine decarboxylase, were evaluated in cultured neuroblastoma and glioma cells. Retinol and retinoic acid arrested the proliferation of neuroblastoma at concentrations of 50 μM; retinal was effective at 5 μM. Glioma cells were 5–10 fold less sensitive to all three analogs. A correlation existed between the inhibition of growth and the inhibition of ornithine decarboxylase in both cell lines treated with the retinoids. Difluoromethyl ornithine did not toally arrest tumor growth at concentrations of 5 mM; however, the antitumor effects were enhanced with the addition of retinol. An earlier and more complete cytostatic response was observed in glioma cells which had been treated with the combination of 100 μM retinol and 5 mM difluoromethyl ornithine than in cells which had been treated with either agent alone. These results show that tumors of neural origin are retinoid sensitive and suggest that a combination of vitamin A analogs and ornithine decarboxylase inhibitors may produce an increased chemotherapeutic response.