Inhibitory effect of hydroxyflutamide plus tamoxifen on oestradiol-induced growth of MCF-7 breast cancer cells.
The antiandrogen flutamide has been reported to exert antiproliferative actions on breast cancer both in vitro and in vivo. Here we study the action of its active metabolite hydroxyflutamide on the oestradiol-induced growth of MCF-7 breast cancer cells. The results show that the antiandrogen inhibits the cell growth. Moreover hydroxyflutamide adds its antiproliferative effect to the action of the antioestrogen tamoxifen. The inhibitory effect is dose-dependent and it is unaffected by tamoxifen concentrations up to levels able to block oestrogen receptors completely. Dihydrotestosterone experiments parallel those on hydroxyflutamide. When the two substances are administered together, neither antagonistic nor additive effects are appreciable. Data are consistent with an androgen-like action of hydroxyflutamide on breast cancer cells. The antiproliferative effect of hydroxyflutamide, without virilizing side-effects, suggests that it is worth exploring its possible employment together with antioestrogens in the treatment of breast cancer patients.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000008:administration & dosage; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005485:Flutamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D013629:Tamoxifen / Q000008:administration & dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004965:Estrogen Antagonists; D013196:Dihydrotestosterone; D013629:Tamoxifen; C014290:hydroxyflutamide; D004958:Estradiol; D005485:Flutamide