The effect of vitamins A and E on neuroblastoma growth and differentiation.

Abstract

The effects of dl-$\alpha$-tocopherol and dl-$\alpha$-tocopheryl succinate on neuroblastoma, N1E 115, cells were studied. Tocopherol had no growth-arresting properties, whereas its succinate ester derivative inhibited growth at concentrations $\ge$20 $\mu$M. The succinate derivative was taken up somewhat more readily than free tocopherol; however, for any equal uptake of both forms of vitamin E, only the succinate derivative could affect growth. Tocopheryl succinate was taken up without marked conversion to tocopherol. The data point to the functionality of the carboxyl group of the succinate derivative as a basis for the difference in potency of the two forms of vitamin E. The succinate derivative of vitamin E was effective in growth inhibition of neuroblastoma, although the mechanism of action appears to involve cytotoxicity rather than induction of differentiation. The effects of retinoic acid on the morphology, the lipid metabolism and protein kinase activities of two related human neuroblastoma cell lines, SK-N-SH-F (SH-F) and SK-N-SH-N (SH-N) were studied. Pulse-chase experiments with both cell lines showed that turnover of arachidonic acid in lipid classes was most rapid in phosphatidylinositol, followed by phosphatidylethanolamine and phosphatidylcholine, and very low in phosphatidylserine. The redistribution of the arachidonic acid label following the chase was found to be markedly different in these variant cell lines. In SH-F the decrease of label in phospholipids was accompanied by an increase in the labelling of triglyceride. In SH-N, this redistribution of label in triglyceride was not observed. Following a six day exposure to retinoic acid, increased arachidonic acid turnover was observed in phosphatidylcholine and phosphatidylserine in SH-F and SH-N cell lines. The effect of retinoic acid on components of signal transduction pathways was investigated. Marked, but opposite, changes in protein kinase C activity were observed in both cell lines following retinoic acid treatment. SH-F cells displayed a substantial increase in protein kinase C activity; and SH-N cells, exhibited a decrease in protein kinase C activity. (Abstract shortened by UMI.)