Send to

Choose Destination
Antioxid Redox Signal. 2007 Nov;9(11):1875-81.

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

Author information

Redox Biology Center and the Biochemistry Department, University of Nebraska, Lincoln, Nebraska, USA.


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center