Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in the culture medium of a well differentiated human prostatic cancer cell (LNCaP) inhibits cellular growth and stimulates PSA secretion. The differentiation of the cells tested was documented by their responsiveness to androgens and the ability to synthesize cellular markers of differentiation (PSA). The raise in cAMP level was produced by dibutyryl cyclic AMP (DBcAMP) or by agents acting at distinct levels in the pathway of cAMP generation (forskolin) or degradation (IBMX). Each of these three agents in a range of concentrations between 10-4-10-6 M had an inhibitory effect on the growth which is dose and time-dependent. The inhibition was reversible as demonstrated by complete restoration of cell growth soon after the withdrawal of the substances from the culture medium. When cAMP levels in culture medium was raised, an increase in PSA content was observed. However, the effects of cAMP on PSA content was not due to increase in PSA synthesis, since simultaneous measurement of secreted and cellular PSA indicated that the principal effect of the cyclic nucleotide was to enhance the secretion of stored PSA. Furthermore the inhibition of cellular growth by cAMP suggests new approaches in prostatic carcinoma therapy.

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