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

Anna Prudova, Matthias Albin, Zachary Bauman, Alexander Lin, Victor Vitvitsky, Ruma Banerjee

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 β-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.

Original languageEnglish
Pages (from-to)1875-1881
Number of pages7
JournalAntioxidants and Redox Signaling
Volume9
Issue number11
DOIs
StatePublished - Oct 1 2007

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