PS-990

PS-990, which is a novel microbial metabolite, induced neurite formation in a murine neuroblastoma cell line, Neuro2A. In the presence of PS-990 at 30 micrograms/ml, significant neurite outgrowth was observed. Cultures maintained for 12 h in the presence of PS-990 resulted in the maximal number of neurite-bearing cells, and then the neurites formed were gradually retracted. The retracted cells again yielded the neurite formation when the cells were exposed again to PS-990. PS-990 inhibited both the cell growth and thymidine incorporation into the cells at the same concentration range. Although the type of neurite formation with PS-990 is similar to that with a cyclic AMP analog and indeed PS-990 has an inhibitory potency against calcium and calmodulin-dependent cyclic nucleotide phosphodiesterase, the intracellular cyclic AMP level was not elevated when treated with PS-990. These results suggest that PS-990 reversibly induces neurite formation with arrest of the cell growth through a mechanism distinct from an increase in the intracellular cyclic AMP concentration.

A novel compound, PS-990, which induces differentiation of neuroblastoma cells, was isolated from the culture broth of a fungus, Acremonium sp. KY12702. PS-990 inhibited brain calcium calmodulin-dependent cyclic nucleotide phosphodiesterase with an IC50 value of 3 micrograms/ml, and markedly induced neurite extension of mouse neuroblastoma, Neuro2A, at concentrations ranging from 10 to 30 micrograms ml.