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Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional

Jinsong Zhang1, Vanda Svehlíková, Yongping Bao

  • 1Nutrition Division, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.

Carcinogenesis
|March 29, 2003
PubMed

Insights

Sulforaphane and selenium (Se) synergistically boost thioredoxin reductase 1 (TrxR1) in liver cancer cells. This combined treatment enhances both TrxR1 gene transcription and protein translation, offering significant cellular protection.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Thioredoxin reductases (TrxRs) are crucial enzymes in cellular redox balance, impacting cell proliferation, apoptosis, and signaling pathways implicated in carcinogenesis.
  • Understanding the regulation of TrxRs is vital for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the regulatory effects of sulforaphane and selenium (Se) on thioredoxin reductase 1 (TrxR1) in human hepatoma HepG2 cells.
  • To elucidate the mechanisms of TrxR1 induction by these compounds, individually and in combination.

Main Methods:

  • Human hepatoma HepG2 cells were treated with sulforaphane and sodium selenite.
  • TrxR1 mRNA levels were assessed using quantitative PCR and actinomycin D (transcription inhibitor).
  • TrxR1 protein levels and enzyme activity were measured, alongside studies involving glutathione synthesis and protein kinase C inhibitors.

Main Results:

  • Sulforaphane induced TrxR1 mRNA transcription up to 4-fold, while selenium primarily enhanced TrxR1 protein translation and activity (2.1-fold and 4.8-fold, respectively).
  • Combined sulforaphane and Se treatment synergistically increased TrxR1 mRNA (6.5-fold), protein (5.5-fold), and activity (13-fold).
  • Selenium was found to delay the degradation of sulforaphane-induced TrxR1 mRNA, and the sulforaphane-mediated induction was dependent on glutathione and protein kinase C.

Conclusions:

  • The combination of sulforaphane and selenium demonstrates a synergistic effect on TrxR1 regulation, involving both transcriptional and translational mechanisms.
  • This synergistic induction significantly protected HepG2 cells against paraquat-induced oxidative stress, highlighting a potential therapeutic strategy.
  • The findings underscore the importance of combined interventions targeting TrxR1 for cancer prevention and treatment.

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