title: Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells.
abstract: The most potent steroid in human prostatic carcinoma LNCaP cells, i.e., dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.
authors.affiliation: Medical Research Council of Canada Group in Molecular Endocrinology, CHUL Research Center, Quebec.
authors.forename: Y
authors.initials: Y
authors.lastname: de Launoit
authors.forename: R
authors.initials: R
authors.lastname: Veilleux
authors.forename: M
authors.initials: M
authors.lastname: Dufour
authors.forename: J
authors.initials: J
authors.lastname: Simard
authors.forename: F
authors.initials: F
authors.lastname: Labrie
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D015113:Androstane-3,17-diol / Q000494:pharmacology; D001667:Binding, Competitive; D002453:Cell Cycle / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D005434:Flow Cytometry; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015741:Metribolone / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020849:Raloxifene Hydrochloride; D013629:Tamoxifen / Q000031:analogs & derivatives; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D004965:Estrogen Antagonists; D010880:Piperidines; D013196:Dihydrotestosterone; D013629:Tamoxifen; C064480:EM 139; D015113:Androstane-3,17-diol; D015741:Metribolone; D004970:Estrone; C014290:hydroxyflutamide; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D005485:Flutamide