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.
Anderson
K M
KM
Department of Medicine, Rush Medical College, Chicago, IL 60612.
Wygodny
J B
JB
Ondrey
F
F
Harris
J
J
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D000001:Calcimycin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004247:DNA / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D010743:Phospholipids; D015117:5,8,11,14-Eicosatetraynoic Acid; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D004247:DNA; D007213:Indomethacin