Finasteride induces apoptosis via Bcl-2, Bcl-xL, Bax and caspase-3 proteins in LNCaP human prostate cancer cell line

Int J Oncol. 2008 Apr;32(4):919-24.

Abstract

We investigated the effects of finasteride, a 5alpha-reductase inhibitor, on cell death machinery through the induction of apoptosis in an in vitro model for prostate cancer. Finasteride treatment of the LNCaP hormone-dependent human prostate cancer cell line caused the loss of cell viability and accelerated apoptosis in a concentration-dependent manner. The contents of immunoreactive procaspase-3 were examined by immunoblot analysis and the results suggest that the apoptosis induced by finasteride involves the increase of caspase-3 activity. Early cell changes that occur during apoptosis are associated with mitochondrial changes mediated by members of the Bcl-2 family of proteins. Therefore, Bcl-2, Bcl-xL and Bax were evaluated by the Western blot analysis. The immunoreactivity for pro-apoptotic Bax was markedly increased whereas antiapoptotic Bcl-2 and Bcl-xL expression was significantly reduced after incubation of cells with finasteride. These findings suggest that finasteride induces apoptosis in LNCaP cells via proteins of the Bcl-2 and caspase family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / physiology*
  • Cell Line, Tumor
  • Cholestenone 5 alpha-Reductase / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Finasteride / pharmacology*
  • Humans
  • Male
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • bcl-2-Associated X Protein / physiology*
  • bcl-X Protein / physiology*

Substances

  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Finasteride
  • Cholestenone 5 alpha-Reductase
  • Caspase 3