Control of the proliferation of prostate cancer cells by an androgen and two antiandrogens. Cell specific sets of responses.
The responses, in terms of cell proliferation and c-myc messenger RNA content, of human prostate cancer cells to androgen-receptor ligands were investigated. Experiments were performed with three types of cells (LNCaP, R2 and MOP) and three compounds (the androgen R 1881 and two anti-androgens: cyproterone acetate, CYPA, and RU 56187). MOP cells were established in the laboratory and the effects of RU 56187 had not been studied in culture. In terms of proliferation, LNCaP was stimulated by the three compounds, R2 was inhibited by R 1881 and RU 56187 but was stimulated by CYPA while MOP was inhibited by the three compounds. In the three types of cells, c-myc messenger RNAs were down regulated by R 1881 and RU 56187 but not by CYPA. The conclusions are: (1) the sets of responses of cell proliferation to three androgen-receptor ligands are cell specific; (2) the control of c-myc messenger RNA by R 1881 and RU 56187 may be related to the inhibition of cell proliferation by these compounds but not to their stimulatory effect on cell proliferation; (3) if prostate tumor cells would respond in vivo to androgens and antiandrogens like in culture, patients with prostate cancer could take benefits of reversible medical castration and sequential prescription of various antiandrogens.
Foury
O
O
INSERM-U 329, Hôpital Debrousse, Lyon, France.
Nicolas
B
B
Joly-Pharaboz
M O
MO
André
J
J
D000726:Androgen Antagonists / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D017373:Cyproterone Acetate / Q000494:pharmacology*; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D015741:Metribolone / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D045165:Testosterone Congeners / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D007093:Imidazoles; D009570:Nitriles; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D045165:Testosterone Congeners; C090226:4-(3,4,4-trimethyl-5-oxo-2-thioxo-1-imidazolidinyl)-2-(trifluoromethyl)benzonitrile; D015741:Metribolone; D017373:Cyproterone Acetate