Jul 9, 2009

Alpha-keto acid metabolites of naturally occurring organoselenium compounds as inhibitors of histone deacetylase in human prostate cancer cells

Cancer Prevention Research
Jeong-In LeeJohn T Pinto

Abstract

Histone deacetylase (HDAC) inhibitors are gaining interest as cancer therapeutic agents. We tested the hypothesis that natural organoselenium compounds might be metabolized to HDAC inhibitors in human prostate cancer cells. Se-Methyl-L-selenocysteine (MSC) and selenomethionine are amino acid components of selenium-enriched yeast. In a cell-free system, glutamine transaminase K (GTK) and L-amino acid oxidase convert MSC to the corresponding alpha-keto acid, beta-methylselenopyruvate (MSP), and L-amino acid oxidase converts selenomethionine to its corresponding alpha-keto acid, alpha-keto-gamma-methylselenobutyrate (KMSB). Although methionine (sulfur analogue of selenomethionine) is an excellent substrate for GTK, selenomethionine is poorly metabolized. Structurally, MSP and KMSB resemble the known HDAC inhibitor butyrate. We examined androgen-responsive LNCaP cells and androgen-independent LNCaP C4-2, PC-3, and DU145 cells and found that these human prostate cancer cells exhibit endogenous GTK activities. In the corresponding cytosolic extracts, the metabolism of MSC was accompanied by the concomitant formation of MSP. In MSP-treated and KMSB-treated prostate cancer cell lines, acetylated histone 3 levels increased within 5 hour...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Prostatic Neoplasms
Histone antigen
Selenium
Keto Acids
Post-Translational Protein Processing
HDAC9 gene
L-Selenomethionine
Organoselenium Compounds
Desmolases

Related Feeds

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.