Selenium compounds inhibit IκB kinase (IKK) and nuclear factor-κB (NF-κB) in prostate cancer cells

Alexander V. Gasparian, Ya Juan Yao, Junxuan Lü, Alexander Y. Yemelyanov, Lyudmila A. Lyakh, Thomas J. Slaga, Irina V. Budunova

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Selenium compounds are potential chemopreventive agents for prostate cancer. There are several proposed mechanisms for their anticancer effect, including enhanced apoptosis of transformed cells. Because the transcription factor nuclear factor-κB (NF-κB) is often constitutively activated in tumors and is a key antiapoptotic factor in mammalian cells, we tested whether selenium inhibited NF-κB activity in prostate cancer cells. In our work, we used sodium selenite and a novel synthetic compound, methylseleninic acid (MSeA), that served as a precursor of the putative active monomethyl metabolite methylselenol. We found that both selenium forms inhibited cell growth and induced apoptosis in DU145 and JCA1 prostate carcinoma cells. Sodium selenite and MeSeA, at the concentrations that induced apoptosis, inhibited NF-κB DNA binding induced by tumor necrosis factor-α and lipopolysaccharide in DU145 and JCA1 prostate cells. Both compounds also inhibited κB.Luciferase reporter activity in prostate cells. A key to NF-κB regulation is the inhibitory κB (IκB) proteins that in response to diverse stimuli are rapidly phosphorylated by IκB kinase complex, ubiquitinated, and undergo degradation, releasing NF-κB factor. We showed that sodium selenite and MSeA inhibited IκB kinase activation and IκB-α phosphorylation and degradation induced by TNF-α and lipopolysaccharide in prostate cells. NF-κB blockage by IκB-α d.n. mutant resulted in the sensitization of prostate carcinoma cells to apoptosis induced by selenium compounds. These results suggest that selenium may target the NF-κB activation pathway to exert, at least in part, its cancer chemopreventive effect in prostate.

Original languageEnglish (US)
Pages (from-to)1079-1087
Number of pages9
JournalMolecular cancer therapeutics
Volume1
Issue number12
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gasparian, A. V., Yao, Y. J., Lü, J., Yemelyanov, A. Y., Lyakh, L. A., Slaga, T. J., & Budunova, I. V. (2002). Selenium compounds inhibit IκB kinase (IKK) and nuclear factor-κB (NF-κB) in prostate cancer cells. Molecular cancer therapeutics, 1(12), 1079-1087.