Antiestrogenic activity of two 11 beta-estradiol derivatives on MCF-7 breast cancer cells.
Two 11 beta-derivatives of estradiol (E2) were tested for their potential antiestrogenic activity in the MCF-7 breast cancer model: one contained a phenoxydimethylaminoethyl side-chain (RU 39,411), the other a pentafluoropentylsulfinyl side-chain (RU 58,668). The former compound displayed mixed estrogenic/antiestrogenic properties, while the latter indicated only an antiestrogenic activity. Both the compounds produced a growth inhibition of MCF-7 cells at doses related to their binding affinity for the estrogen receptor (ER); E2 suppressed this inhibition. The compounds also down-regulated the estrogen binding capacity of the cells but failed to reduce ER mRNA levels, indicating that the grafting of their side-chains prevented this antagonistic effect usually observed with steroidal estrogens. Assessment of ER levels by enzyme immunoassay revealed a marked increase with RU 39,411 and a decrease with RU 58,668; different mechanisms of action should, therefore, be considered. Finally, the estrogenic activity of RU 39,411 was demonstrated by its strong ability to induce synthesis of the progesterone receptor; RU 58,668 failed to display this agonistic activity.
Jin
L
L
Laboratoire J.-C. Heuson de Cancérologie Mammaire, Brussels, Belgium.
Borrás
M
M
Lacroix
M
M
Legros
N
N
Leclercq
G
G
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D006801:Humans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D005466:Fluorocarbons
D000970:Antineoplastic Agents; D004958:Estradiol; D004965:Estrogen Antagonists; C060411:RU 39411; C086511:RU 58668; D005466:Fluorocarbons