title: Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens.
abstract: Antiandrogens are in use alone and in combination with other agents as hormonal therapy for prostate cancer. We conducted studies on the androgen-responsive human prostate cancer cell line LNCaP to determine the direct effects of three antiandrogens (hydroxyflutamide, RU23908, and cyproterone acetate) on hormone-responsive human prostate cancer cells in culture. Dihydrotestosterone (DHT) stimulated the growth of LNCaP cells in a dose-dependent fashion. These cells contained approximately 31,000 high-affinity (Kd = 9 x 10(-10) M) androgen binding sites per cell. In the absence of any androgenic stimulation, all three antiandrogens tested showed agonistic properties by increasing the cell number and uptake of [3H]-thymidine. Competitive uptake studies using [3H]-R1881, a nonmetabolized androgen, showed that the three antiandrogens inhibited specific R1881 uptake with IC50s of 0.9 x 10(-7) M for hydroxyflutamide, 2 x 10(-7) M for RU23908, and 1 x 10(-7) M for cyproterone acetate. It is not known whether these unexpected agonistic effects are due to an altered receptor, previously unmasked agonistic properties of the antiandrogens, or emergence of a hypersensitive clone of cells.
authors.affiliation: Breast Cancer Section, National Cancer Institute, Bethesda, Maryland.
authors.forename: G
authors.initials: G
authors.lastname: Wilding
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: E P
authors.initials: EP
authors.lastname: Gelmann
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000726:Androgen Antagonists