ANTIESTROGENIC ACTIVITY OF 2 11-BETA-ESTRADIOL DERIVATIVES ON MCF-7 BREAST-CANCER CELLS

Two 11 beta-derivatives of estradiol (E(2)) were tested for their pote ntial antiestrogenic activity in the MCF-7 breast cancer model: one co ntained a phenoxydimethylaminoethyl side-chain (RU 39 411), the other a pentafluoropentylsulfinyl side-chain (RU 58 668). The former compoun d displayed mixed estrogenic/antiestrogenic properties, while the latt er indicated only an antiestrogenic activity. Both the compounds produ ced a growth inhibition of MCF-7 cells at doses related to their bindi ng affinity for the estrogen receptor (ER); E(2) suppressed this inhib ition. The compounds also down-regulated the estrogen binding capacity of the cells but fail[ed to reduce ER mRNA levels, indicating that th e grafting of their side-chains prevented this antagonistic effect usu ally observed with steroidal estrogens. Assessment of ER levels by enz yme immunoassay revealed a marked increase with RU 39 411 and a decrea se with RU 58 668; different mechanisms of action should, therefore, b e considered. Finally, the estrogenic activity of RU 39 411 was demons trated by its strong ability to induce synthesis of the progesterone r eceptor; RU 58 668 failed to display this agonistic activity.