Testosterone regulation of homocysteine metabolism modulates redox status in human prostate cancer cells

Antioxid Redox Signal. 2007 Nov;9(11):1875-81. doi: 10.1089/ars.2007.1712.


Clearance of homocysteine via the transsulfuration pathway provides an endogenous route for cysteine synthesis and represents a quantitatively significant source of this amino acid needed for glutathione synthesis. Men have higher plasma levels of total homocysteine than do women, but the mechanism of this sex-dependent difference is not known. In this study, we investigated regulation by testosterone of cystathionine beta-synthase (CBS), which catalyzes the committing step in the transsulfuration pathway. We report that testosterone downregulates CBS expression via a posttranscriptional mechanism in the androgen-responsive prostate cancer cell line, LNCaP. This diminution in CBS levels is accompanied by a decrease in flux through the transsulfuration pathway and by a lower intracellular glutathione concentration. The lower antioxidant capacity in testosterone-treated prostate cancer cells increases their susceptibility to oxidative stress conditions. These results demonstrate regulation of the homocysteine-clearing enzyme, CBS, by testosterone and suggest the potential utility of targeting this enzyme as a chemotherapeutic strategy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Androgens / pharmacology*
  • Catalysis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cystathionine beta-Synthase / analysis
  • Cystathionine beta-Synthase / metabolism
  • Dihydrotestosterone / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Genes, Reporter
  • Glutathione / metabolism
  • Homocysteine / metabolism*
  • Humans
  • Luciferases / metabolism
  • Male
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Processing, Post-Translational
  • Sulfur / metabolism
  • Temperature


  • Androgens
  • Dihydrotestosterone
  • Homocysteine
  • Sulfur
  • Luciferases
  • Cystathionine beta-Synthase
  • Glutathione