Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line

Cancer Lett. 2009 Apr 8;276(1):14-20. doi: 10.1016/j.canlet.2008.10.033. Epub 2008 Dec 16.


Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Genistein / administration & dosage
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Microscopy, Fluorescence
  • Prazosin / administration & dosage
  • Prazosin / analogs & derivatives
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism


  • Vascular Endothelial Growth Factor A
  • Terazosin
  • Genistein
  • Prazosin