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

Climacteric. 2014 Dec;17(6):682-91. doi: 10.3109/13697137.2014.937688. Epub 2014 Sep 19.


Objective: To explore the effect and pathway of phytoestrogens in vitro on the growth of both normal and malignant breast cells.

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 μmol/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 17β-estradiol as well as an evaluation of the differential effects on estrogen receptors (ER) α and β were performed.

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. ERβ 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.

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.


Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Breast / drug effects*
  • Breast Neoplasms / pathology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Female
  • Genistein / pharmacology
  • Humans
  • In Situ Nick-End Labeling
  • MCF-7 Cells
  • Phytoestrogens / pharmacology*
  • Quercetin / pharmacology
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology


  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Phytoestrogens
  • Stilbenes
  • Estradiol
  • Quercetin
  • Genistein
  • Resveratrol