The estrogenic and antiestrogenic activities of droloxifene in human breast cancers.
The effects of a new antiestrogen, droloxifene (DROL, (E)-alpha-[p-[2-(dimethylamino)ethoxy]-phenyl]-alpha'-ethyl-3- stilbenol), on human breast cancer cells in vitro and in vivo were studied. Since phenol red has a binding affinity to the estrogen receptor (ER), we studied the activities of drugs in medium with or without this indicator. Estradiol-17 beta (E2) stimulated the growth of ER-positive breast cancer cells, MCF-7, ZR-75-1 and T-47D, in medium without phenol red, but not in medium containing this indicator. In medium without phenol red, DROL had no marked effects on the growth of MCF-7 and ZR-75-1, but slightly stimulated the growth of T-47D. Tamoxifen (TAM) stimulated the growth of these 3 cells. DROL dose-dependently inhibited the E2-induced stimulation of growth of these cells in medium without phenol red, but TAM inhibited the growth only at high concentrations. The growth of ER-negative breast cancer cells, MDA-MB-231, was not influenced by E2, DROL or TAM. DROL was more effective than TAM against ER-positive Br-10 breast carcinoma in nude mice, but neither drug had effects on ER-negative MX-1 breast carcinoma. These results suggest that DROL shows an antitumor effect on ER-positive breast cancers, being less estrogenic and more antiestrogenic than TAM.
Kawamura
I
I
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Mizota
T
T
Lacey
E
E
Tanaka
Y
Y
Manda
T
T
Shimomura
K
K
Kohsaka
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010637:Phenolsulfonphthalein / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C038345:droloxifene; D004958:Estradiol; D010637:Phenolsulfonphthalein