NO EFFECT OF KININS ON DNA-SYNTHESIS IN LNCAP PROSTATE-CANCER CELLS

1. Prostate has kininogenase activity and expresses members of the tis sue kallikrein gene family. The present study examined the effect of e xogenous and endogenous kinins on growth of LNCaP prostate adenocarcin oma cells. 2. Rate of DNA synthesis was measured by incorporation over 4 h of [H-3]-thymidine into a TCA insoluble fraction of LNCaP cells t hat had been cultured for 24 h. 3. Increased [H-3]-thymidine incorpora tion was seen in response to 10 nmol/L testosterone (+103+/-5 s.e.%), dihydrotestosterone (+113+/-14%) and R1881 (+64+/-10%) (P less than or equal to 0.001; n = 4). 4. In contrast 0.05, 5 and 1000 nmol/L lysyl- bradykinin had no effect (15+/-4, 10+/-9 and 5+/-3 s.e.%, respectively ; n = 7). Des-Arg(9)[Leu(8)]-bradykinin (a B-1 receptor antagonist) an d/or D-Arg-[Hyp(3),Thi(5,8),D-Phe(7)]-bradykinin (a B-2 receptor antag onist), 1 nmol/L, and indomethacin, 5 mu mol/L, also had little or no effect. 5. In conclusion, kallidin and endogenous kinins and prostagla ndins have little or no effect on DNA synthesis and therefore on the g rowth of LNCaP cells in comparison to the two-fold stimulation produce d by androgens.