[CAS NO. 54965-24-1]  Tamoxifen (ICI 46474) Citrate

Tamoxifen displays antitumor effect due to its antiestrogenic activity (ER). Values for the apparent affinity of Tamoxifen for the ER range between 30 and 0.01% of that obtained for estradiol, dependent on different ER source (species), protein concentration and condition used for assay. Binding of Tamoxifen to ER further leads to inhibition expression of estrogen-regulated genes, including growth factors and angiogenic factors secreted by the tumor that may stimulate growth by autocrine or paracrine mechanisms. Tamoxifen also directly induces programmed cell death. Tamoxifen produces an inhibitory effect on MCF-7 cell [H]thymidine incorporation and DNA polymerase activity as well as causing a reduction in DNA content of cultures and cell numbers. This inhibitory effect of Tamoxifen on MCF-7 cell growth can be readily reversed by addition of estradiol to the culture medium. 2 and 6 μM Tamoxifen reduces the proportion of cells in S phase and increases the number of cells in G1. At 10 μM, Tamoxifen causes cell death within 48 hr. Tamoxifen inhibits MCF-7 growth with IC50 of ~10 nM after 10 days treatment. Tamoxifen inhibits plasminogen activator activity of MCF-7, and suppresses estradiol-stimulation of plasminogen activator activity. Tamoxifen also evokes minimal increases in cellular progesterone receptor levels. Tamoxifen is able to inhibit the growth of prostate cancer cell PC3, PC3-M, and DU145 with IC50 ranged from 5.5-10 μM, which is related to its inhibition of protein kinase C and induction of p21(waf1/cip1).