Obiorah Ifeyinwa E, Fan Ping, Jordan V Craig
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
Cancer Prev Res (Phila). 2014 Sep;7(9):939-49. doi: 10.1158/1940-6207.CAPR-14-0061. Epub 2014 Jun 3.
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.
植物雌激素已被作为激素替代疗法的天然替代品及其作为化学预防剂的潜力进行了研究。我们研究了雌马酚、染料木黄酮和香豆雌酚对完全雌激素化的MCF7细胞（模拟围绝经期状态）和长期雌激素剥夺的MCF7:5C细胞（模拟多年雌激素剥夺后女性的绝经后状态）细胞生长的影响，并将其与甾体雌激素：17β雌二醇（E2）和结合马雌激素中存在的马萘雌酮的作用进行了比较。甾体和植物雌激素在生理浓度下诱导MCF7细胞增殖，但抑制MCF7:5C细胞的生长并诱导其凋亡。尽管甾体和植物雌激素诱导雌激素反应性基因，但其抗增殖和凋亡作用是通过雌激素受体介导的。使用小干扰RNA敲低ERα可阻断所有雌激素诱导的凋亡和生长抑制。植物雌激素以与甾体雌激素相当的方式诱导内质网应激和炎症反应应激相关基因。使用地塞米松抑制炎症可阻断甾体和植物雌激素诱导的凋亡和生长抑制以及它们诱导凋亡基因的能力。总之，这表明植物雌激素可能潜在地用作老年绝经后女性的化学预防剂，但由于其抗凋亡作用，与甾体抗炎药联合使用时应谨慎。
