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19406207capr140061-sup-fig3.pdf (136.67 kB)

Supplementary Figure 3 from Breast Cancer Cell Apoptosis with Phytoestrogens Is Dependent on an Estrogen-Deprived State

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posted on 2023-04-03, 19:27 authored by Ifeyinwa E. Obiorah, Ping Fan, V. Craig Jordan

PDF file - 136K, Diverse effects of E2, equilin and phytoestrogens on cell cycle progression. Distribution of the cells through the cell-cycle phases was analyzed by flow cytometry in cells treated with E2(1nM), equilin (1nM), genistein (1?M), equol (1?M), coumestrol (1?M) or control for 24 h,48h and 72h. The percentage of the cells in each phase is calculated using the ModFit software. The y axis represents the number of cells and FL2-A represents the intensity of propidium iodide.

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ARTICLE ABSTRACT

Phytoestrogens have been investigated as natural alternatives to hormone replacement therapy and their potential as chemopreventive agents. We investigated the effects of equol, genistein, and coumestrol on cell growth in fully estrogenized MCF7 cells, simulating the perimenopausal state, and long-term estrogen-deprived MCF7:5C cells, which simulate the postmenopausal state of a woman after years of estrogen deprivation, and compared the effects with that of steroidal estrogens: 17β estradiol (E2) and equilin present in conjugated equine estrogen. Steroidal and phytoestrogens induce proliferation of MCF7 cells at physiologic concentrations but inhibit the growth and induce apoptosis of MCF7:5C cells. Although steroidal and phytoestrogens induce estrogen-responsive genes, their antiproliferative and apoptotic effects are mediated through the estrogen receptor. Knockdown of ERα using siRNA blocks all estrogen-induced apoptosis and growth inhibition. Phytoestrogens induce endoplasmic reticulum stress and inflammatory response stress–related genes in a comparable manner as the steroidal estrogens. Inhibition of inflammation using dexamethasone blocked both steroidal- and phytoestrogen-induced apoptosis and growth inhibition as well as their ability to induce apoptotic genes. Together, this suggests that phytoestrogens can potentially be used as chemopreventive agents in older postmenopausal women but caution should be exercised when used in conjunction with steroidal anti-inflammatory agents due to their antiapoptotic effects. Cancer Prev Res; 7(9); 939–49. ©2014 AACR.

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