Growth inhibition of human prostate tumor cells by an agonist of gonadotrophin-releasing hormone.
The effect of [D-Leu6,des-Gly-NH2(10),Proethylamide9]-GnRH, leuprolide, was determined for the human primary prostate tumor cell line ALVA-31 by in vitro mitogenic assays. Prostate tumor cell proliferation was inhibited up to 50% by leuprolide. Inhibition was not observed in parallel cultures treated with other low molecular weight bioactive peptides. The incorporation and metabolic reduction of testosterone was not affected by concentrations of leuprolide that were inhibitory in the mitogenic assay. Specific high-affinity binding of 125I-labeled leuprolide was also demonstrated on intact tumor cells with an estimated effective median dose (ED50) of < 1 x 10(-9)M. Inhibition of prostate tumor growth was further demonstrated in Balb/c athymic intact and castrate male mice bearing ALVA-31 tumor xenografts following chronic administration of leuprolide. These data clearly demonstrate that leuprolide can inhibit the growth of a human prostate carcinoma cell line. Studies conducted in castrate animals further suggest an alternative mechanism of growth inhibition that appears to be independent of the suppression of steroid hormone biosynthesis by LHRH analogues.
Loop
S M
SM
Research Service, Department of Veterans Affairs Medical Center, Tacoma, WA 98493, USA.
Gorder
C A
CA
Lewis
S M
SM
Saiers
J H
JH
Drivdahl
R H
RH
Ostenson
R C
RC
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000378:metabolism; D014407:Tumor Cells, Cultured
D013739:Testosterone; D016729:Leuprolide