Formononetin induces apoptosis in PC-3 prostate cancer cells through enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway

Nutr Cancer. 2014;66(4):656-61. doi: 10.1080/01635581.2014.894098. Epub 2014 Mar 25.


Formononetin (FN), a bioactive component extracted from the red clover (Trifolium pratense L.), has been long used for treating carcinomas in China. In the present study, we aim to investigate the potential therapeutical effects of FN on cell line of prostatic adenocarcinoma (PC-3) and human prostate epithelial cells (RWPE1). These findings indicated that FN significantly inhibited the cell growth of PC-3 in a dose-dependent manner, but no such effect was observed in RWPE1 cells. The apoptotic counts were effectively increased following the treatments as shown in flow cytometry. The results from Western blotting assay suggested that FN treatment contributed to the reduced Bcl-2 protein level and the elevated Bax expression in PC-3 cells, thereby resulting in the increasing Bax/Bcl-2 ratios. Furthermore, the phosphorylated level of p38 in PC-3 cells was activated through the FN treatment, whereas the endogenous Akt phosphorylation was blocked. Collectively, our findings demonstrate that FN exerts the anticarcinogenic effect on prostate cancer in vitro, in which the underlying mechanisms are associated with enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway, thus triggering apoptosis in tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Isoflavones / pharmacology*
  • Male
  • Phosphorylation
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects*
  • Up-Regulation
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antineoplastic Agents
  • BAX protein, human
  • Isoflavones
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • formononetin
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases