Kinetics and concentration effects of TPA-induced differentiation of cultured human neuroblastoma cells.

SH-SY5Y human neuroblastoma cells differentiate morphologically and biochemically in the presence of 12-0-tetradecanoylphorbol-13-acetate (TPA). The degree of differentiation, as demonstrated by the appearance of cell surface projections, growth inhibition and increase in noradrenalin concentration, was dependent on the TPA concentration and had an optimum at 1.6 X 10(-8) M of TPA. At that concentration neuron specific enolase (NSE) increased to a maximum level after 10 days of culture with no further changes in the NSE level during additional culture for 10 days. In contrast, the noradrenalin concentration reached a maximum after 4 days of TPA treatment and decreased during longer exposures to TPA. Based on the facts that the phorbolester induced differentiation shows stereo specificity and was optimal at the same concentration range as common polypeptide hormones, a putative TPA-hormone receptor interaction is discussed. An opposite effect of TPA on the SH-SY5Y cells, antagonizing the differentiation effect, is further suggested to explain the decrease in differentiation observed at TPA concentrations higher than 1.6 X 10(-8) M.