Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells

Cancer Biol Ther. 2002 May-Jun;1(3):287-90. doi: 10.4161/cbt.83.

Abstract

Selenium is an essential micronutrient that is currently being tested for prostate cancer chemoprevention. In spite of its significant promise as a chemopreventive agent, the molecular mechanisms of selenium-mediated effects remain to be elucidated. Recent evidence suggests that selenium may mediate its chemopreventive effects by inducing apoptosis in human prostate cancer cells. Here we report that selenium-mediated apoptosis appears to involve membrane death receptor, DR5-dependent pathway in human prostate cancer cells. Selenium specifically upregulated DR5 expression but not that of DR4. Selenium upregulation of DR5 was coupled with caspase 8 activation and Bid cleavage thereby suggesting the existence of a potential cross-talk between the DR5 and the mitochondrial pathways. Thus, our results suggest that DR5 is specifically regulated by selenium and its activation may play an important role in selenium-mediated chemoprevention.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Arabidopsis Proteins*
  • BH3 Interacting Domain Death Agonist Protein
  • Blotting, Western
  • Carrier Proteins / metabolism
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Enzyme Activation
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, Dominant
  • Humans
  • Male
  • Mitochondria / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Selenium / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Up-Regulation

Substances

  • Antioxidants
  • Arabidopsis Proteins
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Carrier Proteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases
  • Selenium