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- W2018064946 abstract "Abstract The anti-proliferative effects of the novel vitamin D analogue, EB1089, were assessed in the hormone-dependent breast cancer cell line, MCF-7, in vitro . In the present study, EB1089 was shown to be at least an order of magnitude more potent at inhibiting MCF-7 cell proliferation than the native hormone, lα,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). Treatment of MCF-7 cell cultures with combinations of oestradiol and EB1089 ranging from 5 × 10 −11 m to 5 × 10 −9 m revealed the ability of EB1089 to suppress the mitogenic effects of oestradiol in these cells dose-dependently, as determined by [ 3 H]thymidine incorporation and cell counts. EB1089 also exhibited a significant time- and dose-dependent decrease in MCF-7 oestrogen receptor (ER) concentration, as assessed by ligand binding assay. A fourfold reduction of ER levels by 5 × 10 −9 m EB1089 relative to control ER levels was observed, whilst 5 × 10 −9 m 1,25(OH) 2 D 3 produced a significant but less dramatic decrease in ER levels. In addition, reduction of ER protein in EB1089-treated cell cultures was also demonstrated using an oestrogen receptor enzyme immunoassay. The interaction of EB1089 and anti-oestrogens on the oestradiol-stimulated growth of MCF-7 cells was investigated. The treatment of cell cultures with 5 × 10 −10 m EB1089 in combination with the pure anti-oestrogen, ICI 182,780 (5 × 10 −8 m ), and in the presence of between 5 × 10 −10 m and 5 × 10 −9 m oestradiol, produced an augmented inhibition of MCF-7 cell proliferation compared with the actions of either compound alone. This study demonstrates that EB1089 is a potent anti-proliferative agent of breast cancer cells in vitro , and that part of its mechanism to inhibit cell growth may involve the modulation of ER expression, such that the responsiveness of cells to the growth-stimulatory effects of oestradiol is diminished. This new vitamin D analogue has potential in the treatment of breast cancer. Journal of Endocrinology (1994) 141, 555–563" @default.
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- W2018064946 title "Effects of a new synthetic vitamin D analogue, EB1089, on the oestrogen-responsive growth of human breast cancer cells" @default.
- W2018064946 doi "https://doi.org/10.1677/joe.0.1410555" @default.
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