Alpha-keto acid metabolites of organoselenium compounds inhibit HDAC activity Conference Paper

abstract

• HDAC inhibitors are gaining interest as cancer therapeutic agents. We hypothesized that natural organoselenium compound Semethylselenocysteine (MSC) might be metabolized to an HDAC inhibitor. In a cellfree assay, glutamine transaminase K (GTK) converted MSC to methylselenopyruvate (MSP). Molecular modeling supported the interaction of MSP with zinc in the HDAC pocket. In an in vitro HDAC activity assay, MSP was a competitive inhibitor. In various cancer cell lines, MSP increased acetylated histone levels, and induced cell cycle arrest and/or apoptosis. P21WAF1 was increased at both the mRNA and protein level by MSP, and there was enhanced P21WAF1 promoter activity. This work provides a new paradigm by which organoselenium compounds might protect against prostate, colon, skin and other cancers. Thus, in addition to targeting redoxsensitive signaling molecules, alphaketo acid metabolites of organoselenium compounds might alter HDAC activity and histone acetylation status.

authors

• Dashwood, Roderick

published proceedings

• FASEB JOURNAL

author list (cited authors)

• Nian, H., & Dashwood, R. H.

citation count

• 0

complete list of authors

• Nian, Hui||Dashwood, Roderick H

publication date

• April 2010

publisher

• Wiley  Publisher

published in

• The FASEB Journal  Journal

keywords

• 31 Biological Sciences
• 3101 Biochemistry And Cell Biology
• 32 Biomedical And Clinical Sciences
• 3211 Oncology And Carcinogenesis
• 5 Development Of Treatments And Therapeutic Interventions
• 5.1 Pharmaceuticals
• Cancer
• Genetics
• Prostate Cancer
• Urologic Diseases

Digital Object Identifier (DOI)

• 10.1096/fasebj.24.1_supplement.894.7

start page

• 894.7

end page

• 894.7

volume

• 24

issue

• S1

URL

• http://dx.doi.org/10.1096/fasebj.24.1_supplement.894.7