A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells

Acta Pharmacol Sin. 2008 Sep;29(9):1060-8. doi: 10.1111/j.1745-7254.2008.00831.x.

Abstract

Aim: The aim of the present study was to investigate whether low dose genistein affects the invasion and epithelial mesenchymal transition (EMT) of prostate cancer (PCa) cells.

Methods: Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a, were used in this study. The cell lines were found to process EMT in our previous study. The PCa cells were treated with increasing concentrations, from 0.1 to 75 micromol/L. Proliferation was assessed with 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. EMT was proven by cell morphological transition and the expression changes of EMT-related markers, which were confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling. Transwell invasion assay was used to analyze the invasive potency.

Results: The addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1a viable cell number in a dose-dependent manner (with increasing concentrations from 15 to 75 micromol/L). Less than 15 micromol/L genistein was selected as the low dose concentration, which did not affect cell proliferation. The treatment of cells with low-dose genistein induced the reversal of EMT, which was confirmed by cell morphological transition and the expression changes of EMT-related markers. The reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa cells in vitro.

Conclusion: These results showed that treatment with low-dose genistein may be a potential strategy for the suppression of invasive growth through the reversal of EMT in cancer cells, which justifies the potential use of soybean foods as a practical chemopreventive approach for patients with PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Genistein / pharmacology*
  • Humans
  • Male
  • Neoplasm Invasiveness / pathology
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Anticarcinogenic Agents
  • Tetrazolium Salts
  • Thiazoles
  • Genistein
  • thiazolyl blue