Format

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

1
Redox Biology Center and the Biochemistry Department, University of Nebraska, Lincoln, Nebraska, USA.

Abstract

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.

PMID:
17854288
DOI:
10.1089/ars.2007.1712
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center