Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines

J Cancer Res Clin Oncol. 2000 Aug;126(8):448-54.


Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 microM) with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / prevention & control
  • Cell Cycle / drug effects*
  • Diet
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Eicosapentaenoic Acid / pharmacology*
  • Female
  • Flow Cytometry
  • Genistein / pharmacology*
  • Growth Inhibitors / pharmacology*
  • Humans
  • Insectivora
  • Mice
  • Microscopy, Electron
  • Receptors, Estrogen
  • Tumor Cells, Cultured / drug effects*


  • Growth Inhibitors
  • Receptors, Estrogen
  • Eicosapentaenoic Acid
  • Genistein