Phytoestrogens induce differential effects on both normal and malignant human breast cells in vitro

作者：Chen F P^*; Chien M H

来源：Climacteric, 2014, 17(6): 682-691.

DOI：10.3109/13697137.2014.937688

• PHYTOESTROGENS
• GENISTEIN
• RESVERATROL
• QUERCETIN
• MCF-7 BREAST CANCER CELLS
• MCF-10A NORMAL BREAST CELLS

Objective To explore the effect and pathway of phytoestrogens in vitro on the growth of both normal and malignant breast cells. %26lt;br%26gt;Methods Normal breast MCF-10A cells and breast cancer MCF-7 cells were incubated with 10(-10)-10(-4) mol/l genistein, resveratrol, and quercetin (plasma concentrations in human: 10 nmol/l-10 mu mol/l) for 48 h and were then extracted for a cell proliferation assay (MTT), and for a cell death assay (TUNEL) assay. The proteins involved in the proliferative and apoptotic pathways were evaluated by Western blot analysis. Additionally, a comparison with 17 beta-estradiol as well as an evaluation of the differential effects on estrogen receptors (ER) alpha and beta were performed. %26lt;br%26gt;Results MCF-7 cell proliferation was significantly inhibited at the concentrations greater than 10(-4) mol/l for all three phytoestrogens and from 10(-5) mol/l for resveratrol and quercetin. MCF-10A cell proliferation was significantly increased at the concentrations from 10(-8) to 10(-5) mol/l for genistein and resveratrol and only at 10(-5) mol/l for quercetin. Apoptotic cells were significantly increased by these phytoestrogens in the MCF-7 cells. At a concentration of 10(-7) mol/l of these phytoestrogens, a significant reduction of PI3K and Akt and an increase of Fas ligand, Fas-associated protein with death domain, cytochrome C, truncated Bid, caspase-9, and caspase-3 were noted in the MCF-7; PI3K and Akt were significantly increased in the MCF-10A. ER beta expression was significantly elevated in MCF-10A and MCF-7 with these phytoestrogens. The effects of estradiol on normal and malignant breast cells were completely opposite to those of phytoestrogens. %26lt;br%26gt;Conclusions This study demonstrates that phytoestrogens have antiproliferative effects on breast cancer cells via an ER-dependent mechanism, even at low concentrations, but are also capable of maintaining the survival of normal breast cell via ER-independent or other mechanisms.

• 出版日期2014-12
• 单位长春大学