Disease relevance of Ici 164384

• It is concluded that ICI 164384 inhibits breast cancer cell proliferation by inducing a transition delay in G1 phase and that the point of action of this pure estrogen antagonist in early G1 phase is indistinguishable temporally from that of nonsteroidal antiestrogens and calmodulin antagonists [1].
• At non-cytotoxic concentrations, ICI 164384 potentiated the cytotoxicity of doxorubicin in a dose-dependent manner in both the classical multi-drug resistant (MDR) human leukaemia cell lines CEM/VLB 100 and CEM/VLB 1000 and the human small cell lung cancer cell line H69 LX4 [2].

High impact information on Ici 164384

• The estrogen receptor antagonist ICI 164384 had no effect on 17 beta-estradiol-induced relaxations [3].
• Under these conditions, ICI 164384 and LY 117018 had no effect on either cell proliferation or TGF-alpha expression [4].
• We addressed this question in vitro by testing the ability of ectopic cyclin D1 overexpression to overcome the growth-inhibitory effects of tamoxifen and the pure steroidal antiestrogens, ICI 164384 and ICI 182780, in T-47D and MCF-7 human breast cancer cells [5].
• Overall, the data presented in this report support the usefulness of cell fusion to clarify the mechanisms involved in development of resistance to the pure antiestrogens ICI 182780 and ICI 164384 and the selective ER modulator tamoxifen and suggest IGF-IRalpha as a new sensitive marker for response to antiestrogen treatment [6].
• However, following either RA or ICI 164384, there was a reduction in the amount of hyperphosphorylated pRB, first apparent well before cell cycle changes were seen [7].

Chemical compound and disease context of Ici 164384

• Using T-47D human breast cancer cells, we compared the effects of retinoic acid (RA) and the antiestrogen ICI 164384 on cell cycle phase distribution and the expression of genes with known functions in cell cycle control [7].
• The antiestrogen ICI 164384 as well as tamoxifen and its metabolites inhibit estrone sulfatase via noncompetitive mechanisms at Kis ranging from 11-1130 microM in rat breast tumors [8].

Biological context of Ici 164384

• In comparative studies at concentrations ranging from 1.25 to 10 mumols/l, ICI 164384 was significantly more effective (1.2-6-fold) than tamoxifen in reducing the IC50 of doxorubicin in the CEM/VLB 100 line [2].
• Moreover, this enhancement of transcriptional activation by COUP-TFI requires specifically the AF-1 transactivation function of ER and can be observed in the presence of E2 or 4-hydroxytamoxifen but not ICI 164384 [9].

Anatomical context of Ici 164384

• ICI 164384 had no effect on the two respective parental cell lines, CEM/CCRF and H69 P [2].
• The compound ICI 164384 was devoid of oestrogenic activity in the uterus and vagina of both species and on the hypothalamic-pituitary axis of the rat [10].

Gene context of Ici 164384

• In addition, the ER alpha antagonist ICI-164384 is a potent antagonist for ER beta as well [11].
• The antiestrogen ICI 164384 also transiently decreased the steady state mRNA levels of both IGFBP 4 and IGFBP 5 [12].
• This is the first report on repression of components of the extracellular matrix by estradiol and induction by the complete antiestrogen ICI 164384 [13].
• In contrast, the presence of ICI 164384, which does not induce the selection of resistant subclones under the same experimental conditions in which TAM does, may improve the efficacy of low concentration of beta-IFN and prevent the development of a secondary TAM-induced resistance [14].
• Pretreatment of MCF-7 cells for 2 days with either OH TAM or ICI 164384 did not inhibit EGF-induced increases in cell proliferation [15].

References