Antiestrogenic properties of keoxifene, trans-4-hydroxytamoxifen, and ICI 164384, a new steroidal antiestrogen, in ZR-75-1 human breast cancer cells.

摘要: The agonistic/antagonistic properties of two non-steroidal antiestrogens, namelytrans-4-monohydroxy-tamoxifen (OH-TAM) and keoxifene (LY156758), the new steroidal antiestrogen ICI164384, a 7β-alkylamide derivative estradiol (E2), were assessed by measuring their effect on proliferation ZR·75-1 cells, an estrogen-responsive human breast cancer cell line. While subnanomolar concentrations both OH-TAM LY156758 had significant estrogenic stimulatory activity growth in absence estrogens higher inhibitory, ICI164384 behaved exclusively as inhibitor more potently so than other compounds. three antiestrogens similar potency to inhibit mitogenic E2 at 300 nM, all antiproliferative effects completely reversible estrogen. was weaker competitor of3H-labeled or R2858 (moxestrol) uptake intact ZR-75-1 cells 1-hour assay, partly because slower intracellular access estrogen specific binding sites. Moreover, interacted rapidly (~ 6 h) manner with estrogen-specific sites, while induced longer-acting (> 24 down-regulation [3H]R2858 uptake. present data indicate that, among studied, is only compound acting pure behave endowed partial agonistic this system.