Human PC-3 prostate cell line DNA synthesis is suppressed by eicosatetraynoic acid, an in vitro inhibitor of arachidonic acid metabolism.

When human PC-3 cells derived from a metastatic prostatic adenocarcinoma were incubated for 15 min to 4 h with the in vitro inhibitor of eicosanoid biosynthesis, eicosatetraynoic acid (ETYA) at 10-80 microM, DNA synthesis was suppressed. No reduction in cellular viability occurred, as judged by exclusion of trypan blue or unaltered release of 51Cr-labeled proteins, and the inhibition was partially reversible. Indomethacin (to 12.5 micrograms/ml) did not inhibit DNA synthesis or alter the suppression of DNA synthesis by ETYA, suggesting a role for a lipoxygenase product in this effect. Addition of leukotriene B4 (LTB4) at 10(-8) M did not reverse the inhibition of DNA synthesis produced by ETYA, nor did arachidonic acid (10(-5) - 10(-9) M) incubated with control cells mimic the effect of that agent. 3H-arachidonic acid incubated with PC-3 cells was rapidly incorporated into phospholipids and this labeling was differentially inhibited by ETYA. Positive modulation of PC-3 cellular DNA synthesis by lipoxygenase products and inhibition of their synthesis by ETYA is one attractive hypothesis with which to account for these results. Other consequences of producing a selective deficiency of arachidonic acid in cellular membrane phospholipids and even the probable substitution of ETYA for arachidonic acid could also contribute to the inhibition of DNA synthesis by ETYA.