Stimulation of neurotrophic factor secretion from 1321N1 human astrocytoma cells by novel diterpenoids, scabronines A and G.

Glial cells release neurotrophic factors that maintain neurons functionally. When rat pheochromocytoma cells (PC-12) were cultivated with the conditioned medium of human astrocytoma cells (1321N1) incubated with the new diterpenoids, scabronines A and G, isolated from Sarcodon scabrosus, they changed their morphology and there was neurite outgrowth. The scabronines increased the expression of mRNA for nerve growth factor (NGF), and the secretion of NGF from 1321N1 cells in a concentration-dependent manner. However, the enhanced neurite outgrowth produced by the conditioned media was slightly inhibited by NGF neutralizing antibody, and the concentration of NGF released in response to the scabronines was insufficient to cause differentiation. These results suggest that scabronines cause the secretion of other factors together with NGF from 1321N1 cells. The diterpenoids are useful drugs to clarify the mechanism of synthesis and secretion of neurotrophic factors.