Antiestrogenic DTACs inhibit estrogen receptor alpha-mediated transcription.

2004 DEC 2 - (NewsRx.com & NewsRx.net) -- Antiestrogenic DTACs inhibit estrogen receptor alpha-mediated transcription.

According to a study from the United States, "A novel class of pure antiestrogens, 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), lack estrogenic activity in a mouse uterotrophic assay and inhibit the growth of estrogen-sensitive MCF-7 breast cancer cells (Day et al., 1991).

"Reporter assays were used to evaluate the effects of the DTACs on estrogen receptor alpha(ERalpha)-mediated transcription from either classic estrogen-response elements (EREs) or nonclassic AP-1 elements."

"Among the DTACs tested," reported P. Cheng and coworkers, "only the compounds with smaller aromatic substituents, BDRM72 and BDRM81, displayed weak agonist activity on EREs. Their activity was less than that observed for the ER partial agonist, 4-hydroxytamoxifen (ZOHT)."

"In competition experiments, the DTACs blocked estradiol-stimulated transcription from an ERE in a dose-dependent manner and were more effective inhibitors than ZOHT. Each of the DTACs was significantly less active than ZOHT or the pure antiestrogen ICI 182,780 faslodex) in stimulating transcription from nonclassic AP-1 elements in the presence of ERalpha.

"DTACs did not modulate either basal or TPA (12-O-tetradecanoylphorbol-13-acetate)-stimulated transcription from an AP-1 element in the absence of ERalpha," the authors continued, "indicating that they are not nonspecific inhibitors of transcription and ...